Is BRCA2 p.Arg2502Gly (c.7504C>G) pathogenic?

BRCA2 p.Arg2502Gly (c.7504C>G) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: likely benign (0.1071); Absent from gnomAD v4.1; Associated with Hereditary cancer.

What condition is associated with BRCA2 p.Arg2502Gly (c.7504C>G)?

BRCA2 p.Arg2502Gly (c.7504C>G) is associated with Hereditary cancer (ClinVar).

How common is BRCA2 p.Arg2502Gly (c.7504C>G) in the general population?

BRCA2 p.Arg2502Gly (c.7504C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Arg2502Gly (c.7504C>G)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

BRCA2 p.Arg2502Gly

c.7504C>G · VCV3764509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Hereditary cancer

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.455	indeterminate
Splicing
SpliceAI	Δ0.20	acceptor loss, 15 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.2	GERP 0.54
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	6.339	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.Arg2502Gly
Coding: c.7504C>G
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32356496 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2502: a UniProt-annotated variant site (in bc; uncertain significance); a UniProt-annotated variant site (in); the 'interaction with fancd2' region; the 'interaction with sem1' region

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

Disease context

Hereditary cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Arg2502His Benign ★★★ same residue
BRCA2 p.Arg2502Cys Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Arg2502Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Arg2502Pro Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Arg2502Ser Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Arg2502= Likely benign ★ same residue
BRCA2 p.Arg2502fs Pathogenic ★★★ same residue
BRCA2 c.6841+5G>A Uncertain significance ★★ 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-arg2502gly (accessed [today's date]).

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