Is BRCA2 p.Asp596= (c.1788T>C) pathogenic?

BRCA2 p.Asp596= (c.1788T>C) is classified Benign in BRCA2 (ClinVar, Expert panel, 28 submitters; last evaluated 2015-01-12). Low-frequency (popmax 2.34%, afr); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Asp596= (c.1788T>C)?

BRCA2 p.Asp596= (c.1788T>C) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Asp596= (c.1788T>C) in the general population?

BRCA2 p.Asp596= (c.1788T>C) is low-frequency (popmax 2.34%, 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.Asp596=

c.1788T>C · rs11571642 · VCV51193

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 28 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.34%, 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 0.61	GERP -1.8, phastCons 1
Overall
CADD	6.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.34% African / African-American · 1,743/74,552 alleles

Filtering AF 2.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.21%

Overall 0.137% 2,198/1,608,580 alleles · low-frequency exomes 1,108/1,456,372 · genomes 1,090/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.34%	43
Ashkenazi Jewishnot grpmax-eligible	0.51%	196
Admixed American	0.22%	454
Remaining individualsnot grpmax-eligible	0.19%	527
Middle Eastern	0.0663%	1,507
European (non-Finnish)	0.00441%	22,653
South Asian	0.00112%	89,680

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.Asp596=
Coding: c.1788T>C
MANE Select: NM_000059
dbSNP: rs11571642
Type: single nucleotide variant
Location: chr13:32333266 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

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 Fanconi anemia complementation group D1 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.Asp596His Benign ★★★ same residue
BRCA2 p.Asp596Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp596Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp596Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asp596fs Pathogenic ★★★ 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-asp596 (accessed [today's date]).

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