Is BRCA1 p.Cys47Phe (c.140G>T) pathogenic?

BRCA1 p.Cys47Phe (c.140G>T) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2025-03-04). AlphaMissense: likely pathogenic (0.9945); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Cys47Phe (c.140G>T)?

BRCA1 p.Cys47Phe (c.140G>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Cys47Phe (c.140G>T) in the general population?

BRCA1 p.Cys47Phe (c.140G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Cys47Phe (c.140G>T)?

AlphaMissense predicts likely pathogenic (score 0.9945) — an in-silico prediction, not a clinical call.

BRCA1 p.Cys47Phe

c.140G>T · rs80357150 · VCV54247

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely pathogenic

0.9945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9945	likely pathogenic ✓ concordant with ClinVar · top 1% in BRCA1
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -15.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	24.8	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.Cys47Phe
Coding: c.140G>T
MANE Select: NM_007294
dbSNP: rs80357150
Type: single nucleotide variant
Location: chr17:43106528 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1 hereditary breast carcinoma

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.Cys47Gly Likely pathogenic ★ same residue
BRCA1 p.Cys47Ser 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-cys47phe (accessed [today's date]).

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