--- title: "BRCA1 C44F (c.131G>T, rs80357446) | Dante Labs" description: "ClinVar classifies BRCA1 C44F 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/brca1/variants/c44f" --- 1. [Genes](https://dantelabs.com/genes) 2. [BRCA1](https://dantelabs.com/genes/brca1) 3. BRCA1 C44F Variant # BRCA1 C44F NM_007294.4(BRCA1):c.131G>T (p.Cys44Phe) Also known as - 250G>T - p.Cys44Phe - p.C44F - rs80357446 * ClinVar classification Pathogenic * Review status 3 stars out of 4 reviewed by expert panel * Last evaluated 18 June 2019 * Expert panel Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Data current to ClinVar release 2026-10-12 · Dante Labs data release 2026.10.19-9814e911 Facts last changed 19 October 2026 ## Summary C44F is a missense variant in BRCA1: it changes a single amino acid in the protein the gene encodes. ClinVar classifies it as pathogenic for breast-ovarian cancer, familial, susceptibility to, 1 (reviewed by expert panel). ## ClinVar classifications | Condition | Classification | Review status | Submissions | Last evaluated | | ------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------- | ----------------------------------------- | ------------ | -------------- | | breast-ovarian cancer, familial, susceptibility to, 1[ClinVar VCV000054200 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/54200/) | Pathogenic | 3 stars out of 4 reviewed by expert panel | 1 submission | 18 June 2019 | Classifications as ClinVar records them in release 2026-10-12. ClinVar updates them as evidence is reviewed. ## ACMG/AMP criteria The ACMG/AMP criteria C44F meets, from its predicted effect in BRCA1, gnomAD and ClinVar. | Criterion | Strength | Points | Rests on | | -------------------------------------------------------- | ---------- | ----------- | --------------------------------------------------------------------------------- | | PM5 A different pathogenic change at the same amino acid | Moderate | +2 | p.Cys44Ser at the same amino acid, ClinVar: Pathogenic (reviewed by expert panel) | | PP5 A reputable source reports it as pathogenic | Supporting | Not counted | ClinVar: Pathogenic (reviewed by expert panel) | On these criteria alone: +2 points, uncertain significance. Assessed automatically, without functional, computational or family evidence. Not a clinical classification. ## Population frequency How often C44F is seen among the people whose exomes and genomes gnomAD 4.1 brings together. | Dataset | Allele frequency | Allele count | Homozygotes | Commonest in | | -------------- | --------------------- | -------------- | ----------- | ---------------------- | | gnomAD exomes | 0.00021% 1 in 487,056 | 3 of 1,461,168 | 0 | Middle Eastern: 0.017% | | 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. [C44F in the gnomAD browser (opens in a new tab)](https://gnomad.broadinstitute.org/variant/17-43115729-C-A?dataset=gnomad_r4) ## Where it lies in BRCA1 C44F lies in exon 3 of the 23 in BRCA1's MANE Select transcript, NM_007294.4. [BRCA1 variants in exon 3 →](https://dantelabs.com/genes/brca1/variants?exon=3) [BRCA1's gene diagram →](https://dantelabs.com/genes/brca1#gene-structure) ## Molecular details | Gene | [BRCA1](https://dantelabs.com/genes/brca1) | | --------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------- | | Transcript | NM_007294.4 MANE Select | | Coding DNA change (HGVS c.) | c.131G>T | | Protein change (HGVS p.) | p.Cys44Phe p.C44F | | Predicted consequence | Missense [missense_variant (opens in a new tab)](https://purl.obolibrary.org/obo/SO_0001583) | | Predicted impact | Moderate | | Position (GRCh38) | chr17:43115729 C>A | | Position (GRCh37) | chr17:41267746 C>A | | dbSNP ID | [rs80357446 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs80357446) | | ClinVar Variation ID | [VCV000054200 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/54200/) | | ClinVar Allele ID | 68867 | | ClinGen Allele Registry ID | [CA000862 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA000862) | | ClinVar name | NM_007294.4(BRCA1):c.131G>T (p.Cys44Phe) | | Other names | 250G>T | ## BRCA1 C44F in other databases - [ClinVar VCV000054200 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/clinvar/variation/54200/) - [dbSNP rs80357446 (opens in a new tab)](https://www.ncbi.nlm.nih.gov/snp/rs80357446) - [ClinGen Allele Registry CA000862 (opens in a new tab)](https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA000862) - [gnomAD 17-43115729-C-A (opens in a new tab)](https://gnomad.broadinstitute.org/variant/17-43115729-C-A?dataset=gnomad_r4) - [Ensembl rs80357446 (opens in a new tab)](https://www.ensembl.org/Homo_sapiens/Variation/Explore?v=rs80357446) ## Reports that look at this variant (1) These Genome Test condition reports include C44F among the variants they look at. | Report | Conditions | Inheritance | | ------------------------------------------------------------------------------------------------------------------- | --------------------------------------------- | ------------------ | | [Hereditary Breast and Ovarian Cancer (BRCA1/2)](https://dantelabs.com/conditions/hereditary-breast-ovarian-cancer) | Hereditary Breast and Ovarian Cancer Syndrome | Autosomal dominant | | | BRCA1-related cancer predisposition | Autosomal dominant | ## Other variants in BRCA1 - [A92Ffs\*4 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a92ffs4) - [A134Qfs\*7 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a134qfs7) - [A302Cfs\*2 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a302cfs2) - [A302Lfs\*12 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a302lfs12) - [A322Kfs\*2 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a322kfs2) - [A322Lfs\*19 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a322lfs19) - [A407Sfs\*5 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a407sfs5) - [A433Pfs\*8 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a433pfs8) - [A469Qfs\*6 Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a469qfs6) - [A521X Pathogenic 3 stars out of 4](https://dantelabs.com/genes/brca1/variants/a521x) [All BRCA1 variants](https://dantelabs.com/genes/brca1/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 2026-10-19-c4908f54). - Reference SNP identifiers from dbSNP (release b157), National Center for Biotechnology Information. - Gene–disease links from the Gene Curation Coalition, GenCC (release 2026-10-19). - 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 2026.10.19-9814e911 of 19 October 2026. ## Cite this page APA > Dante Labs. (19 October 2026). BRCA1 C44F (c.131G>T, rs80357446) (Version 2026.10.19-9814e911). Retrieved 21 October 2026, from https\://dantelabs.com/genes/brca1/variants/c44f Vancouver > Dante Labs. BRCA1 C44F (c.131G>T, rs80357446) \[Internet]. Version 2026.10.19-9814e911. 19 October 2026 \[cited 21 October 2026]. Available from: https\://dantelabs.com/genes/brca1/variants/c44f Download citation [RIS](https://dantelabs.com/genes/brca1/variants/c44f/cite.ris) [BibTeX](https://dantelabs.com/genes/brca1/variants/c44f/cite.bib) [CSL-JSON](https://dantelabs.com/genes/brca1/variants/c44f/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)