Is BRCA2 p.Gln2829Pro (c.8486A>C) pathogenic?

BRCA2 p.Gln2829Pro (c.8486A>C) is classified Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely pathogenic (0.8259); Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Gln2829Pro (c.8486A>C)?

BRCA2 p.Gln2829Pro (c.8486A>C) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Gln2829Pro (c.8486A>C) in the general population?

BRCA2 p.Gln2829Pro (c.8486A>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.Gln2829Pro (c.8486A>C)?

AlphaMissense predicts likely pathogenic (score 0.8259) — an in-silico prediction, not a clinical call.

BRCA2 p.Gln2829Pro

c.8486A>C · rs80359100 · VCV1484629

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8259 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.8259	likely pathogenic ✓ concordant with ClinVar · top 3% in BRCA2
REVEL	0.529	indeterminate
Splicing
SpliceAI	Δ0.30	donor loss, 1 bp away · raw score · deltas
Pangolin	Δ0.43	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	27.2	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: BRCA2
Protein: p.Gln2829Pro
Coding: c.8486A>C
MANE Select: NM_000059
dbSNP: rs80359100
Type: single nucleotide variant
Location: chr13:32370556 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2829: the 'interaction with sem1' region

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.Gln2829Arg Pathogenic ★★★ ⚠ same residue
BRCA2 p.Gln2829Ter Pathogenic ★★★ same residue
BRCA2 p.Gln2829His Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Gln2829Lys Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Gln2829fs Pathogenic ★ same residue
BRCA2 p.Gln2829= Uncertain significance ★ same residue
BRCA2 p.Gln2829Leu Uncertain significance 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-gln2829pro (accessed [today's date]).

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