Is BRCA1 p.Pro977= (c.2931A>G) pathogenic?

BRCA1 p.Pro977= (c.2931A>G) is classified Likely benign in BRCA1 (ClinVar, Expert panel, 10 submitters; last evaluated 2017-06-29). Ultra-rare (popmax 0.0133%, amr); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Pro977= (c.2931A>G)?

BRCA1 p.Pro977= (c.2931A>G) is associated with breast-ovarian cancer, familial, susceptibility to, 1, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Pro977= (c.2931A>G) in the general population?

BRCA1 p.Pro977= (c.2931A>G) is ultra-rare (popmax 0.0133%, amr) (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.

BRCA1 p.Pro977=

c.2931A>G · rs273899691 · VCV54725

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -4.8
Overall
CADD	0.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,994 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000889% 13/1,461,822 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,499
East Asian	0.00892%	11,216
European (non-Finnish)	8.47e-05%	1,180,012

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA1
Protein: p.Pro977=
Coding: c.2931A>G
MANE Select: NM_007294
dbSNP: rs273899691
Type: single nucleotide variant
Location: chr17:43092600 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 977: a UniProt-annotated variant site (in fancs)

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

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Pro977Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro977Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro977Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro977fs Pathogenic/Likely pathogenic ★★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T Pathogenic ★★★ same condition
BRCA1 c.212+1G>A Pathogenic ★★★ same condition
BRCA1 c.212+1G>T 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-pro977 (accessed [today's date]).

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