Is BRCA2 p.Pro3292= (c.9876G>A) pathogenic?

BRCA2 p.Pro3292= (c.9876G>A) is classified Likely benign in BRCA2 (ClinVar, Expert panel, 16 submitters; last evaluated 2017-06-29). Ultra-rare (popmax 0.0707%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Pro3292= (c.9876G>A)?

BRCA2 p.Pro3292= (c.9876G>A) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, medulloblastoma (ClinVar).

How common is BRCA2 p.Pro3292= (c.9876G>A) in the general population?

BRCA2 p.Pro3292= (c.9876G>A) is ultra-rare (popmax 0.0707%, afr) (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.

BRCA2 p.Pro3292=

c.9876G>A · rs369047997 · VCV182304

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0707%, afr)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.87	GERP -4.7
Overall
CADD	15.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0707% African / African-American · 53/75,008 alleles

Filtering AF 0.0554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0501%

Overall 0.00527% 85/1,614,082 alleles · ultra-rare exomes 49/1,461,870 · genomes 36/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0707%	1,415
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	0.0022%	45,386

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.Pro3292=
Coding: c.9876G>A
MANE Select: NM_000059
dbSNP: rs369047997
Type: single nucleotide variant
Location: chr13:32398389 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 3292: the 'tr2 region' region; a turn

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

Disease context

breast-ovarian cancer, familial, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome medulloblastoma prostate cancer Wilms tumor 1 Fanconi anemia complementation group D1 glioma susceptibility 3 pancreatic cancer, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Pro3292Leu Benign ★★★ same residue
BRCA2 p.Pro3292Ala Uncertain significance ★★ ⚠ same residue
BRCA2 p.Pro3292Gln Uncertain significance ★★ ⚠ same residue
BRCA2 p.Pro3292Ser Uncertain significance ★★ ⚠ same residue
BRCA2 p.Pro3292Thr 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

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-pro3292 (accessed [today's date]).

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