Is BRCA2 p.Pro1088= (c.3264T>C) pathogenic?

BRCA2 p.Pro1088= (c.3264T>C) is classified Benign in BRCA2 (ClinVar, Expert panel, 34 submitters; last evaluated 2015-01-12). Low-frequency (popmax 2.49%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Pro1088= (c.3264T>C)?

BRCA2 p.Pro1088= (c.3264T>C) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Pro1088= (c.3264T>C) in the general population?

BRCA2 p.Pro1088= (c.3264T>C) is low-frequency (popmax 2.49%, 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.Pro1088=

c.3264T>C · rs36060526 · VCV51435

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 34 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.49%, afr)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

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 -0.29, phastCons 0.07
Overall
CADD	2.352	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.49% African / African-American · 1,838/73,706 alleles

Filtering AF 2.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.132% 2,099/1,589,920 alleles · low-frequency exomes 1,002/1,437,650 · genomes 1,097/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.49%	40
Remaining individualsnot grpmax-eligible	0.176%	568
Admixed American	0.159%	630
Middle Eastern	0.0676%	1,480
South Asian	0.0115%	8,665
European (non-Finnish)	0.00427%	23,393
East Asian	0.00224%	44,662

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.Pro1088=
Coding: c.3264T>C
MANE Select: NM_000059
dbSNP: rs36060526
Type: single nucleotide variant
Location: chr13:32337619 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1088: the 'interaction with rad51' region

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 breast cancer 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.Pro1088Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Pro1088His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Pro1088Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Pro1088Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Pro1088Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Pro1088fs Pathogenic ★★★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>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-pro1088 (accessed [today's date]).

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