Is BRCA2 p.Asp156Gly (c.467A>G) pathogenic?

BRCA2 p.Asp156Gly (c.467A>G) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 21 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.1114); Ultra-rare (popmax 0.0547%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Asp156Gly (c.467A>G)?

BRCA2 p.Asp156Gly (c.467A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, medulloblastoma (ClinVar).

How common is BRCA2 p.Asp156Gly (c.467A>G) in the general population?

BRCA2 p.Asp156Gly (c.467A>G) is ultra-rare (popmax 0.0547%, afr) (gnomAD).

What do computational predictors say about BRCA2 p.Asp156Gly (c.467A>G)?

AlphaMissense predicts likely benign (score 0.1114) — an in-silico prediction, not a clinical call.

BRCA2 p.Asp156Gly

c.467A>G · rs68071147 · VCV51694

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 21 submitters

AlphaMissense

likely benign

0.1114 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0547%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1114	likely benign
REVEL	0.237	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	Δ0.97	donor gain, 1 bp away · raw score · deltas
Pangolin	Δ0.86	gain · loss 0.43 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.8	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	26.6	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 0.0547% African / African-American · 41/74,930 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00367% 59/1,609,358 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0547%	1,828
Admixed American	0.005%	20,007
Remaining individualsnot grpmax-eligible	0.00482%	20,767
South Asian	0.0011%	90,892
European (non-Finnish)	0.000935%	106,975

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.Asp156Gly
Coding: c.467A>G
MANE Select: NM_000059
dbSNP: rs68071147
Type: single nucleotide variant
Location: chr13:32326142 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

BRCA2 p.Asp156Ala Uncertain significance ★★ ⚠ same residue
BRCA2 p.Asp156Val Uncertain significance ★★ ⚠ same residue
BRCA2 p.Asp156= Likely benign ★★ same residue
BRCA2 p.Asp156Asn Uncertain significance ★ ⚠ same residue
BRCA2 p.Asp156Glu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Asp156Ter 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-asp156gly (accessed [today's date]).

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