Is BRCA1 p.Cys47Ser (c.139T>A) pathogenic?

BRCA1 p.Cys47Ser (c.139T>A) is classified Pathogenic in BRCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2015-10-02). AlphaMissense: likely pathogenic (0.9969); Absent from gnomAD v4.1; Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Cys47Ser (c.139T>A)?

BRCA1 p.Cys47Ser (c.139T>A) is associated with breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Cys47Ser (c.139T>A) in the general population?

BRCA1 p.Cys47Ser (c.139T>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BRCA1 p.Cys47Ser (c.139T>A)?

AlphaMissense predicts likely pathogenic (score 0.9969) — an in-silico prediction, not a clinical call.

BRCA1 p.Cys47Ser

c.139T>A · rs80357370 · VCV267508

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.9969	likely pathogenic ✓ concordant with ClinVar · top 1% in BRCA1
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -12.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.27	acceptor loss · deltas
Pangolin	Δ0.39	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA1
Protein: p.Cys47Ser
Coding: c.139T>A
MANE Select: NM_007294
dbSNP: rs80357370
Type: single nucleotide variant
Location: chr17:43106529 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Cys47Ter Pathogenic ★★★ same residue
BRCA1 p.Cys47Tyr Pathogenic ★★★ same residue
BRCA1 p.Cys47= Likely benign ★★★ same residue
BRCA1 p.Cys47Arg Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Cys47Phe Pathogenic/Likely pathogenic ★★ same residue
BRCA1 p.Cys47Gly Likely pathogenic ★ same residue
BRCA1 p.Cys47fs Pathogenic ★★★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brca1-p-cys47ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown