--- title: "ADA E255X (c.763G>T, rs2123517896) | Dante Labs" description: "ClinVar classifies ADA E255X as Likely pathogenic (reviewed by expert panel). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/ada/variants/e255x" --- 1. [Genes](https://dantelabs.com/genes) 2. [ADA](https://dantelabs.com/genes/ada) 3. ADA E255X Variant # ADA E255X NM_000022.4(ADA):c.763G>T (p.Glu255Ter) Also known as - p.Glu255Ter - p.E255\* - rs2123517896 * ClinVar classification Likely pathogenic * Review status 3 stars out of 4 reviewed by expert panel * Last evaluated 5 February 2024 * Expert panel ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen Data current to ClinVar release 2026-10-19 · Dante Labs data release 2026.10.21-311f020e Facts last changed 21 October 2026 ## Summary E255X is a nonsense variant in ADA: it creates an early stop signal, so the protein the gene encodes is predicted to be cut short. ClinVar classifies it as likely pathogenic for severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency (reviewed by expert panel). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | ----------------- | ----------------------------------------- | ------------ | --------------- | | severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-negative, due to adenosine deaminase deficiency[ClinVar VCV001335461 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/1335461/) | Likely pathogenic | 3 stars out of 4 reviewed by expert panel | 1 submission | 5 February 2024 | Classifications as ClinVar records them in release 2026-10-19. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria E255X meets, from its predicted effect in ADA, gnomAD and ClinVar. | Criterion | Strength | Points | Rests on | | ------------------------------------------------------- | ----------- | ----------- | ------------------------------------------------------------------- | | PVS1 Null variant where loss of function causes disease | Very strong | +8 | stop_gained on NM_000022.4Expected to cause nonsense-mediated decay | | PM2 Absent or very rare in population databases | Supporting | +1 | Not seen in gnomAD exomes, gnomAD genomes | | PP5 A reputable source reports it as pathogenic | Supporting | Not counted | ClinVar: Likely pathogenic (reviewed by expert panel) | On these criteria alone: +9 points, likely pathogenic. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## ClinGen expert panel classifications How ClinGen's expert panels have classified E255X, applying the ACMG/AMP criteria with their own gene rules and evidence. | Condition | Expert panel | Classification | Criteria applied | Approved | | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | --------------------------------------------- | ----------------- | ------------------------------------ | --------------- | | adenosine deaminase deficiency[ClinGen Evidence Repository (opens in a new tab)](https://erepo.genome.network/evrepo/ui/classification/94f76e8a-75fa-420e-a438-336ac5b850e1) | Severe Combined Immunodeficiency Disease VCEP | Likely pathogenic | PVS1 (Very strong), PM2 (Supporting) | 5 February 2024 | As published in the ClinGen Evidence Repository. Expert panels' classifications are kept apart from the criteria above and do not change them. ## Population frequency How often E255X is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | ---------------- | ------------ | ----------- | ------------ | | gnomAD exomes | Not seen | 0 of 0 | 0 | | | gnomAD genomes | Not seen | 0 of 0 | 0 | | Figures from gnomAD 4.1, as gnomAD publishes them. Groups are genetic ancestry groups as gnomAD infers them. They describe the variant in gnomAD's populations, not anyone's result. [E255X in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/20-44622846-C-A?dataset=gnomad_r4) ## Molecular details | Gene | [ADA](https://dantelabs.com/genes/ada) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000022.4 MANE Select | | Coding DNA change (HGVS c.) | c.763G>T | | Protein change (HGVS p.) | p.Glu255Ter p.E255\* | | Predicted consequence | Nonsense (stop gained) [stop_gained (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001587) | | Predicted impact | High | | Position (GRCh38) | chr20:44622846 C>A | | Position (GRCh37) | chr20:43251487 C>A | | dbSNP ID | [rs2123517896 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs2123517896) | | ClinVar Variation ID | [VCV001335461 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/1335461/) | | ClinVar Allele ID | 1326432 | | ClinGen Allele Registry ID | [CA409120184 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA409120184) | | ClinVar name | NM_000022.4(ADA):c.763G>T (p.Glu255Ter) | ## ADA E255X in other databases - [ClinVar VCV001335461 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/1335461/) - [dbSNP rs2123517896 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs2123517896) - [ClinGen Allele Registry CA409120184 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA409120184) - [gnomAD 20-44622846-C-A (opens in a new tab)](https://gnomad.broadinstitute.org/variant/20-44622846-C-A?dataset=gnomad_r4) - [Ensembl rs2123517896 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs2123517896) ## Reports that look at this variant (2) These Genome Test condition reports include E255X among the variants they look at. | Report | Conditions | Inheritance | | ----------------------------------------------------------------------------------------------------- | -------------------------------- | ------------------- | | [Other Inborn Errors of Immunity](https://dantelabs.com/conditions/immunodeficiency-disease) | Immunodeficiency Disease | | | [Severe Combined Immunodeficiency](https://dantelabs.com/conditions/severe-combined-immunodeficiency) | Severe Combined Immunodeficiency | Autosomal recessive | ## Other variants in ADA - [A329V Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/a329v) - [c.219-2A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-219-2a-g) - [c.363-2A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-363-2a-g) - [c.603C>A Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-603c-a) - [c.606+1G>T Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-606plus1g-t) - [c.975+1G>A Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-975plus1g-a) - [c.976-1G>C Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-976-1g-c) - [c.1078+2T>A Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/c-1078plus2t-a) - [G216R Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/g216r) - [G239D Pathogenic 3 stars out of 4](https://dantelabs.com/genes/ada/variants/g239d) [All ADA variants](https://dantelabs.com/genes/ada/variants) ## Limitations This page describes publicly available information about a genetic variant. It is not a diagnosis, and it says nothing about whether you or anyone else carries this variant. Classifications come from ClinVar and change as new evidence is reviewed. A classification here may differ from the one in ClinVar today, or from the one a laboratory reports. Whole genome sequencing with short reads can miss or miscall some variants, particularly in repeated or highly similar stretches of DNA and in large insertions, deletions or rearrangements. If you have questions about a variant in your own results or in your family, talk to a genetic counsellor or your doctor. ## Sources & credits - Classifications from ClinVar (release 2026-10-19), National Center for Biotechnology Information. - Condition terms from the Mondo Disease Ontology (release 2026-10-06), used under CC BY 4.0. - Gene symbols and names from the HUGO Gene Nomenclature Committee (release 2026-10-16). - Allele identifiers from the ClinGen Allele Registry (release 2026-10-21-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-21). - Difficult regions from the Genome in a Bottle Consortium (release v3.6). - Transcripts from MANE (release v1.5), NCBI and EMBL-EBI. - Predicted consequences from mehari (release 0.11.0), with transcript models from cdot. - Built from Dante Labs data release 2026.10.21-311f020e of 21 October 2026. ## Cite this page APA > Dante Labs. (21 October 2026). ADA E255X (c.763G>T, rs2123517896) (Version 2026.10.21-311f020e). Retrieved 21 October 2026, from https\://dantelabs.com/genes/ada/variants/e255x Vancouver > Dante Labs. ADA E255X (c.763G>T, rs2123517896) \[Internet]. Version 2026.10.21-311f020e. 21 October 2026 \[cited 21 October 2026]. Available from: https\://dantelabs.com/genes/ada/variants/e255x Download citation [RIS](https://dantelabs.com/genes/ada/variants/e255x/cite.ris) [BibTeX](https://dantelabs.com/genes/ada/variants/e255x/cite.bib) [CSL-JSON](https://dantelabs.com/genes/ada/variants/e255x/cite.json) ## Read your whole genome From $449 Free shipping · Results in 6–8 weeks [Explore the Genome Test](https://dantelabs.com/whole-genome-sequencing)