--- title: "PMS2 C331X (c.993C>A, rs186577215) | Dante Labs" description: "ClinVar classifies PMS2 C331X as Pathogenic/likely pathogenic (criteria provided, multiple submitters, no conflicts). Where it sits in the genome, its predicted effect, and the Genome Test reports that look at it." url: "https://dantelabs.com/genes/pms2/variants/c331x" --- 1. [Genes](https://dantelabs.com/genes) 2. [PMS2](https://dantelabs.com/genes/pms2) 3. PMS2 C331X Variant # PMS2 C331X NM_000535.7(PMS2):c.993C>A (p.Cys331Ter) Also known as - p.Cys331Ter - p.C331\* - rs186577215 * ClinVar classification Pathogenic/likely pathogenic * Review status 2 stars out of 4 criteria provided, multiple submitters, no conflicts * Last evaluated 11 January 2024 Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.16-c6eea6bf Facts last changed 16 October 2026 ## Summary C331X is a nonsense variant in PMS2: it creates an early stop signal, so the protein the gene encodes is predicted to be cut short. ClinVar classifies it as pathogenic or likely pathogenic for Lynch syndrome 4 (criteria provided, multiple submitters, no conflicts). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | -------------------------------------------------------------------------------------------------------------------- | ---------------------------- | --------------------------------------------------------------------- | ------------- | --------------- | | Lynch syndrome 4[ClinVar VCV001768663 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/1768663/) | Pathogenic/likely pathogenic | 2 stars out of 4 criteria provided, multiple submitters, no conflicts | 2 submissions | 11 January 2024 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## Where it lies in PMS2 C331X lies in exon 10 of the 15 in PMS2's MANE Select transcript, NM_000535.7. [PMS2 variants in exon 10 →](https://dantelabs.com/genes/pms2/variants?exon=10) [PMS2's gene diagram →](https://dantelabs.com/genes/pms2#gene-structure) ## Molecular details | Gene | [PMS2](https://dantelabs.com/genes/pms2) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000535.7 MANE Select | | Coding DNA change (HGVS c.) | c.993C>A | | Protein change (HGVS p.) | p.Cys331Ter p.C331\* | | Predicted consequence | Nonsense (stop gained) [stop_gained (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001587) | | Predicted impact | High | | Position (GRCh38) | chr7:5989951 G>T | | Position (GRCh37) | chr7:6029582 G>T | | dbSNP ID | [rs186577215 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs186577215) | | ClinVar Variation ID | [VCV001768663 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/1768663/) | | ClinVar Allele ID | 1829072 | | ClinGen Allele Registry ID | [CA366743034 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA366743034) | | ClinVar name | NM_000535.7(PMS2):c.993C>A (p.Cys331Ter) | ## PMS2 C331X in other databases - [ClinVar VCV001768663 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/1768663/) - [dbSNP rs186577215 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs186577215) - [ClinGen Allele Registry CA366743034 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA366743034) - [gnomAD 7-5989951-G-T (opens in a new tab)](https://gnomad.broadinstitute.org/variant/7-5989951-G-T?dataset=gnomad_r4) - [Ensembl rs186577215 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs186577215) ## Reports that look at this variant (1) These Genome Test condition reports include C331X among the variants they look at. | Report | Conditions | Inheritance | | ----------------------------------------------------------------- | -------------- | ------------------ | | [Lynch Syndrome](https://dantelabs.com/conditions/lynch-syndrome) | Lynch Syndrome | Autosomal dominant | ## Other variants in PMS2 - [c.1A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-1a-g) - [c.24-12_107delinsAAAT Pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-24-12to107delinsaaat) - [c.163+2T>C Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-163plus2t-c) - [c.164-2A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-164-2a-g) - [c.164-518_803+252delinsCG Pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-164-518to803plus252delinscg) - [c.251-2A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-251-2a-g) - [c.538-478_705+456del Pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-538-478to705plus456del) - [c.705+1G>T Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-705plus1g-t) - [c.989-2A>G Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-989-2a-g) - [c.989-296_1144+706del Pathogenic 3 stars out of 4](https://dantelabs.com/genes/pms2/variants/c-989-296to1144plus706del) [All PMS2 variants](https://dantelabs.com/genes/pms2/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 2026-10-12), 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 2026-10-16-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-16). - 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 2026.10.16-c6eea6bf of 16 October 2026. ## Cite this page APA > Dante Labs. (16 October 2026). PMS2 C331X (c.993C>A, rs186577215) (Version 2026.10.16-c6eea6bf). Retrieved 17 October 2026, from https\://dantelabs.com/genes/pms2/variants/c331x Vancouver > Dante Labs. PMS2 C331X (c.993C>A, rs186577215) \[Internet]. Version 2026.10.16-c6eea6bf. 16 October 2026 \[cited 17 October 2026]. Available from: https\://dantelabs.com/genes/pms2/variants/c331x Download citation [RIS](https://dantelabs.com/genes/pms2/variants/c331x/cite.ris) [BibTeX](https://dantelabs.com/genes/pms2/variants/c331x/cite.bib) [CSL-JSON](https://dantelabs.com/genes/pms2/variants/c331x/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)