Is BRCA1 p.Pro897Ala (c.2689C>G) pathogenic?

BRCA1 p.Pro897Ala (c.2689C>G) is classified Likely benign in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-01). AlphaMissense: likely benign (0.0997); Very rare (popmax 0.0022%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Pro897Ala (c.2689C>G)?

BRCA1 p.Pro897Ala (c.2689C>G) is associated with breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Pro897Ala (c.2689C>G) in the general population?

BRCA1 p.Pro897Ala (c.2689C>G) is very rare (popmax 0.0022%, sas) (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.Pro897Ala (c.2689C>G)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

BRCA1 p.Pro897Ala

c.2689C>G · VCV4856501

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.433	indeterminate
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.75, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	14.19	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 0.0022% South Asian · 2/91,060 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,613,812 alleles · very rare exomes 2/1,461,686 · genomes 0/152,126 · joint denominator

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.Pro897Ala
Coding: c.2689C>G
MANE Select: NM_007294
Type: single nucleotide variant
Location: chr17:43092842 (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.Pro897Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro897fs Pathogenic ★★★ same residue
BRCA1 p.Pro897Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Pro897= Likely 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

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-pro897ala (accessed [today's date]).

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