Is BRCA1 p.Gly275Asp (c.824G>A) pathogenic?

BRCA1 p.Gly275Asp (c.824G>A) is classified Benign in BRCA1 (ClinVar, Expert panel, 21 submitters; last evaluated 2019-06-18). AlphaMissense: likely benign (0.328); Rare (popmax 0.127%, eas); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Gly275Asp (c.824G>A)?

BRCA1 p.Gly275Asp (c.824G>A) is associated with breast-ovarian cancer, familial, susceptibility to, 1, hereditary breast ovarian cancer syndrome, pancreatic cancer, susceptibility to, 4 (ClinVar).

How common is BRCA1 p.Gly275Asp (c.824G>A) in the general population?

BRCA1 p.Gly275Asp (c.824G>A) is rare (popmax 0.127%, eas) (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.Gly275Asp (c.824G>A)?

AlphaMissense predicts likely benign (score 0.328) — an in-silico prediction, not a clinical call.

BRCA1 p.Gly275Asp

c.824G>A · rs397509327 · VCV55726

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 21 submitters

AlphaMissense

likely benign

0.328 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.328	likely benign
REVEL	0.691	pathogenic-leaning
SaProt	LLR -5.90	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 0.127% East Asian · 57/44,852 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0912%

Overall 0.00354% 57/1,611,772 alleles · rare

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.Gly275Asp
Coding: c.824G>A
MANE Select: NM_007294
dbSNP: rs397509327
Type: single nucleotide variant
Location: chr17:43094707 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 275: a UniProt-annotated variant site (in)

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 pancreatic cancer, susceptibility to, 4 familial pancreatic carcinoma hereditary neoplastic syndrome hereditary breast carcinoma breast neoplasm Fanconi anemia, complementation group S

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Gly275= Likely benign ★★★ same residue
BRCA1 p.Gly275Ser Benign ★★★ ⚠ 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
BRCA1 c.212+3A>G Pathogenic ★★★ same condition
BRCA1 c.213-12A>G 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-gly275asp (accessed [today's date]).

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