Is BRCA2 p.Pro835= (c.2505A>G) pathogenic?

BRCA2 p.Pro835= (c.2505A>G) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-18). No allele count reported in gnomAD v4.1 (AN 1,609,964); Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Pro835= (c.2505A>G)?

BRCA2 p.Pro835= (c.2505A>G) is associated with BRCA2-related cancer predisposition (ClinVar).

How common is BRCA2 p.Pro835= (c.2505A>G) in the general population?

BRCA2 p.Pro835= (c.2505A>G) is no allele count reported in gnomAD v4.1 (AN 1,609,964) (gnomAD).

BRCA2 p.Pro835=

c.2505A>G · VCV3778933

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,964)

Conditions

BRCA2-related cancer predisposition

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 1.5	GERP -4.6
Overall
CADD	0.993	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,964). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Pro835=
Coding: c.2505A>G
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32336860 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 835: the 'interaction with npm1' region

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

Disease context

BRCA2-related cancer predisposition — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Pro835Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Pro835Thr Uncertain significance ★ ⚠ same residue
BRCA2 p.Pro835Ser Likely benign ★ same residue
BRCA2 c.517-2A>G Pathogenic ★★★ same condition
BRCA2 c.631+2T>G Pathogenic ★★★ same condition
BRCA2 c.631+4A>G Likely pathogenic ★★★ same condition
BRCA2 c.632-3C>G Likely pathogenic ★★★ same condition
BRCA2 c.6938-2A>G 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-pro835 (accessed [today's date]).

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