--- title: "TP53 R280S (c.840A>T, rs1567547687) | Dante Labs" description: "ClinVar classifies TP53 R280S as 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/tp53/variants/r280s" --- 1. [Genes](https://dantelabs.com/genes) 2. [TP53](https://dantelabs.com/genes/tp53) 3. TP53 R280S Variant # TP53 R280S NM_000546.6(TP53):c.840A>T (p.Arg280Ser) Also known as - p.Arg280Ser - p.R280S - rs1567547687 * ClinVar classification Pathogenic * Review status 3 stars out of 4 reviewed by expert panel * Last evaluated 2 April 2026 * Expert panel ClinGen TP53 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 R280S is a missense variant in TP53: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic for Li-Fraumeni Syndrome (reviewed by expert panel). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------- | ----------------------------------------- | ------------ | -------------- | | [Li-Fraumeni Syndrome](https://dantelabs.com/conditions/li-fraumeni-syndrome) [ClinVar VCV000988616 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/988616/) | Pathogenic | 3 stars out of 4 reviewed by expert panel | 1 submission | 2 April 2026 | Classifications as ClinVar records them in release 2026-10-19. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria R280S meets, from its predicted effect in TP53, gnomAD and ClinVar. | Criterion | Strength | Points | Rests on | | -------------------------------------------------- | ---------- | ----------- | -------------------------------------------------------------------------------------------------------------------------------- | | PS1 Same amino acid change as a pathogenic variant | Strong | +4 | p.Arg280Ser at the same amino acid, ClinVar: Pathogenic/likely pathogenic (criteria provided, multiple submitters, no conflicts) | | PP5 A reputable source reports it as pathogenic | Supporting | Not counted | ClinVar: Pathogenic (reviewed by expert panel) | On these criteria alone: +4 points, uncertain significance. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## ClinGen expert panel classifications How ClinGen's expert panels have classified R280S, applying the ACMG/AMP criteria with their own gene rules and evidence. | Condition | Expert panel | Classification | Criteria applied | Approved | | ------------------------------------------------------------------------------------------------------------------------------------------------------------------ | ------------ | -------------- | -------------------------------------------------------------------------------- | ------------ | | Li-Fraumeni syndrome[ClinGen Evidence Repository (opens in a new tab)](https://erepo.genome.network/evrepo/ui/classification/54ad9d59-0134-41c7-92ef-3b86fb2181d5) | TP53 VCEP | Pathogenic | PP4 (Moderate), PP3 (Moderate), PM2 (Supporting), PS3 (Strong), PM1 (Supporting) | 2 April 2026 | 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 R280S 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 | 0.00066% 1 in 152,024 | 1 of 152,024 | 0 | European (non-Finnish): 0.0015% | 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. [R280S in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/17-7673780-T-A?dataset=gnomad_r4) ## Where it lies in TP53 R280S lies in exon 8 of the 11 in TP53's MANE Select transcript, NM_000546.6. [TP53 variants in exon 8 →](https://dantelabs.com/genes/tp53/variants?exon=8) [TP53's gene diagram →](https://dantelabs.com/genes/tp53#gene-structure) ## Molecular details | Gene | [TP53](https://dantelabs.com/genes/tp53) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_000546.6 MANE Select | | Coding DNA change (HGVS c.) | c.840A>T | | Protein change (HGVS p.) | p.Arg280Ser p.R280S | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr17:7673780 T>A | | Position (GRCh37) | chr17:7577098 T>A | | dbSNP ID | [rs1567547687 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs1567547687) | | ClinVar Variation ID | [VCV000988616 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/988616/) | | ClinVar Allele ID | 976547 | | ClinGen Allele Registry ID | [CA397836831 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA397836831) | | ClinVar name | NM_000546.6(TP53):c.840A>T (p.Arg280Ser) | ## TP53 R280S in other databases - [ClinVar VCV000988616 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/988616/) - [dbSNP rs1567547687 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs1567547687) - [ClinGen Allele Registry CA397836831 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA397836831) - [gnomAD 17-7673780-T-A (opens in a new tab)](https://gnomad.broadinstitute.org/variant/17-7673780-T-A?dataset=gnomad_r4) - [Ensembl rs1567547687 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs1567547687) ## Reports that look at this variant (1) These Genome Test condition reports include R280S among the variants they look at. | Report | Conditions | Inheritance | | ----------------------------------------------------------------------------- | -------------------- | ------------------ | | [Li-Fraumeni Syndrome](https://dantelabs.com/conditions/li-fraumeni-syndrome) | Li-Fraumeni Syndrome | Autosomal dominant | ## Other variants in TP53 - [A138P Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/a138p) - [A138V Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/a138v) - [A161_Y163delinsD Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/a161-y163delinsd) - [A347D Pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/a347d) - [c.-29+1G>T Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/c--29plus1g-t) - [c.97-1G>A Pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/c-97-1g-a) - [c.375+5G>A Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/c-375plus5g-a) - [c.919+1G>A Pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/c-919plus1g-a) - [c.993+1del Likely pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/c-993plus1del) - [C124X Pathogenic 3 stars out of 4](https://dantelabs.com/genes/tp53/variants/c124x) [All TP53 variants](https://dantelabs.com/genes/tp53/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). TP53 R280S (c.840A>T, rs1567547687) (Version 2026.10.21-311f020e). Retrieved 21 October 2026, from https\://dantelabs.com/genes/tp53/variants/r280s Vancouver > Dante Labs. TP53 R280S (c.840A>T, rs1567547687) \[Internet]. Version 2026.10.21-311f020e. 21 October 2026 \[cited 21 October 2026]. Available from: https\://dantelabs.com/genes/tp53/variants/r280s Download citation [RIS](https://dantelabs.com/genes/tp53/variants/r280s/cite.ris) [BibTeX](https://dantelabs.com/genes/tp53/variants/r280s/cite.bib) [CSL-JSON](https://dantelabs.com/genes/tp53/variants/r280s/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)