Is BRCA2 p.Arg2896Pro (c.8687G>C) pathogenic?

BRCA2 p.Arg2896Pro (c.8687G>C) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-11). AlphaMissense: ambiguous (0.5408); Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Arg2896Pro (c.8687G>C)?

BRCA2 p.Arg2896Pro (c.8687G>C) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Arg2896Pro (c.8687G>C) in the general population?

BRCA2 p.Arg2896Pro (c.8687G>C) is absent from gnomAD v4.1 (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 BRCA2 p.Arg2896Pro (c.8687G>C)?

AlphaMissense predicts ambiguous (score 0.5408) — an in-silico prediction, not a clinical call.

BRCA2 p.Arg2896Pro

c.8687G>C · rs80359128 · VCV1721425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5408 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.5408	ambiguous · top 8% in BRCA2
REVEL	0.276	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.83	GERP -4.2
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	11.25	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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: BRCA2
Protein: p.Arg2896Pro
Coding: c.8687G>C
MANE Select: NM_000059
dbSNP: rs80359128
Type: single nucleotide variant
Location: chr13:32376724 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — 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

BRCA2 p.Arg2896Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg2896Gly Uncertain significance ★ ⚠ same residue
BRCA2 p.Arg2896His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg2896Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg2896fs Pathogenic ★ same residue
BRCA2 p.Arg2896= Likely benign ★★★ same residue
BRCA2 p.Arg2896Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.316+2T>C 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/brca2-p-arg2896pro (accessed [today's date]).

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