Is BRCA2 p.Arg2500= (c.7500G>A) pathogenic?

BRCA2 p.Arg2500= (c.7500G>A) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-03). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Arg2500= (c.7500G>A)?

BRCA2 p.Arg2500= (c.7500G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Arg2500= (c.7500G>A) in the general population?

BRCA2 p.Arg2500= (c.7500G>A) is absent from gnomAD v4.1 (gnomAD).

BRCA2 p.Arg2500=

c.7500G>A · rs2072696646 · VCV1759216

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.23	GERP -1.6, phastCons 0.042
Overall
CADD	5.681	PHRED · no single calibrated threshold — expert panels disagree

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.Arg2500=
Coding: c.7500G>A
MANE Select: NM_000059
dbSNP: rs2072696646
Type: single nucleotide variant
Location: chr13:32356492 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2500: 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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Arg2500Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Arg2500Thr Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Arg2500fs Pathogenic ★★ same residue
BRCA2 p.Arg2500Ser Uncertain significance ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>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-arg2500 (accessed [today's date]).

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