Is BRCA2 p.Gln713Leu (c.2138A>T) pathogenic?

BRCA2 p.Gln713Leu (c.2138A>T) is classified Benign/Likely benign in BRCA2 (ClinVar, Multiple submitters, 27 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1166); Rare (popmax 0.452%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Gln713Leu (c.2138A>T)?

BRCA2 p.Gln713Leu (c.2138A>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Gln713Leu (c.2138A>T) in the general population?

BRCA2 p.Gln713Leu (c.2138A>T) is rare (popmax 0.452%, afr) (gnomAD).

What do computational predictors say about BRCA2 p.Gln713Leu (c.2138A>T)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

BRCA2 p.Gln713Leu

c.2138A>T · rs55816687 · VCV51249

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 27 submitters

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.452%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.274	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.5, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	14.51	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.452% African / African-American · 339/75,064 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.396%

Overall 0.0224% 362/1,614,142 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.452%	221
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.015%	6,667

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.Gln713Leu
Coding: c.2138A>T
MANE Select: NM_000059
dbSNP: rs55816687
Type: single nucleotide variant
Location: chr13:32336493 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 713: the 'interaction with npm1' 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

Also linked: hereditary breast ovarian cancer syndrome breast cancer breast-ovarian cancer, familial, susceptibility to, 2 breast neoplasm

Similar variants

BRCA2 p.Gln713Ter Pathogenic ★★★ same residue
BRCA2 p.Gln713Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Gln713= Likely benign ★ same residue
BRCA2 p.Gln713Pro Likely benign ★ same residue
BRCA2 p.Gln713fs 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-gln713leu (accessed [today's date]).

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