Is BRCA2 p.Gln2829Arg (c.8486A>G) pathogenic?

BRCA2 p.Gln2829Arg (c.8486A>G) is classified Pathogenic in BRCA2 (ClinVar, Expert panel, 16 submitters; last evaluated 2026-09-21). AlphaMissense: likely benign (0.2474); Very rare (popmax 8.51e-05%, nfe); Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Gln2829Arg (c.8486A>G)?

BRCA2 p.Gln2829Arg (c.8486A>G) is associated with BRCA2-related cancer predisposition, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Gln2829Arg (c.8486A>G) in the general population?

BRCA2 p.Gln2829Arg (c.8486A>G) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Gln2829Arg (c.8486A>G)?

AlphaMissense predicts likely benign (score 0.2474) — an in-silico prediction, not a clinical call.

BRCA2 p.Gln2829Arg

c.8486A>G · rs80359100 · VCV38161

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.2474 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.2474	likely benign ⚠ discordant with ClinVar
REVEL	0.422	indeterminate
Splicing
SpliceAI	Δ0.36	donor loss, 1 bp away · raw score · deltas
Pangolin	Δ0.50	loss · gain 0.03 · 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	27.4	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 8.51e-05% European (non-Finnish) · 1/1,175,124 alleles

Overall 6.87e-05% 1/1,456,384 alleles · very 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: BRCA2
Protein: p.Gln2829Arg
Coding: c.8486A>G
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

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome

Similar variants

BRCA2 p.Gln2829Ter Pathogenic ★★★ same residue
BRCA2 p.Gln2829His Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Gln2829Pro Likely pathogenic ★★ same residue
BRCA2 p.Gln2829Lys Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Gln2829Leu Uncertain significance same residue
BRCA2 p.Gln2829fs Pathogenic ★ same residue
BRCA2 p.Gln2829= Uncertain significance ★ same residue
BRCA2 c.316+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/brca2-p-gln2829arg (accessed [today's date]).

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