Is BRCA1 p.Asp96Gly (c.287A>G) pathogenic?

BRCA1 p.Asp96Gly (c.287A>G) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-10-22). AlphaMissense: likely pathogenic (0.9201); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Asp96Gly (c.287A>G)?

BRCA1 p.Asp96Gly (c.287A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Asp96Gly (c.287A>G) in the general population?

BRCA1 p.Asp96Gly (c.287A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Asp96Gly (c.287A>G)?

AlphaMissense predicts likely pathogenic (score 0.9201) — an in-silico prediction, not a clinical call.

BRCA1 p.Asp96Gly

c.287A>G · rs864622444 · VCV220258

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9201 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9201	likely pathogenic ✓ concordant with ClinVar · top 3% in BRCA1
REVEL	0.809	moderately pathogenic-leaning
SaProt	LLR -5.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	25.8	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.Asp96Gly
Coding: c.287A>G
MANE Select: NM_007294
dbSNP: rs864622444
Type: single nucleotide variant
Location: chr17:43104882 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 96: an α-helix

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 pancreatic cancer, susceptibility to, 4 hereditary breast carcinoma Fanconi anemia, complementation group S

Similar variants

BRCA1 p.Asp96Asn Likely pathogenic ★★★ ⚠ same residue
BRCA1 p.Asp96= Likely benign ★★★ same residue
BRCA1 p.Asp96Val Pathogenic/Likely pathogenic ★★ ⚠ same residue
BRCA1 p.Asp96Ala Likely pathogenic ★ ⚠ same residue
BRCA1 p.Asp96Glu Uncertain significance ★ ⚠ same residue
BRCA1 p.Asp96His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp96fs Pathogenic/Likely 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-asp96gly (accessed [today's date]).

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