Is BRCA2 p.Asp23Glu (c.69T>G) pathogenic?

BRCA2 p.Asp23Glu (c.69T>G) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-23). AlphaMissense: ambiguous (0.529); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Asp23Glu (c.69T>G)?

BRCA2 p.Asp23Glu (c.69T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Asp23Glu (c.69T>G) in the general population?

BRCA2 p.Asp23Glu (c.69T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA2 p.Asp23Glu (c.69T>G)?

AlphaMissense predicts ambiguous (score 0.529) — an in-silico prediction, not a clinical call.

BRCA2 p.Asp23Glu

c.69T>G · VCV4757662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.529 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.529	ambiguous · top 8% in BRCA2
REVEL	0.066	moderately benign-leaning
Splicing
SpliceAI	Δ0.22	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP -0.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	21.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA2
Protein: p.Asp23Glu
Coding: c.69T>G
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32319078 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 23: the 'interaction with palb2' 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

Similar variants

BRCA2 p.Asp23Asn Uncertain significance ★★★ ⚠ same residue
BRCA2 p.Asp23Gly Uncertain significance ★★ ⚠ same residue
BRCA2 p.Asp23= Likely benign ★★ same residue
BRCA2 p.Asp23Val Uncertain significance ★ ⚠ same residue
BRCA2 p.Asp23_Leu24insTer Pathogenic ★★★ same residue
BRCA2 p.Asp23Tyr Pathogenic/Likely pathogenic ★★ ⚠ same residue
BRCA2 p.Asp23His Uncertain significance ★ ⚠ same residue
BRCA2 c.316+1G>T 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-asp23glu (accessed [today's date]).

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