Is BRCA2 p.Ala1588= (c.4764C>T) pathogenic?

BRCA2 p.Ala1588= (c.4764C>T) is classified Uncertain significance in BRCA2 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD v4.1; Associated with breast cancer.

What condition is associated with BRCA2 p.Ala1588= (c.4764C>T)?

BRCA2 p.Ala1588= (c.4764C>T) is associated with breast cancer (ClinVar).

How common is BRCA2 p.Ala1588= (c.4764C>T) in the general population?

BRCA2 p.Ala1588= (c.4764C>T) is absent from gnomAD v4.1 (gnomAD).

BRCA2 p.Ala1588=

c.4764C>T · rs2137509962 · VCV1049602

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

breast cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.21	GERP -4.9
Overall
CADD	0.823	PHRED · no single calibrated threshold — expert panels disagree

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.Ala1588=
Coding: c.4764C>T
MANE Select: NM_000059
dbSNP: rs2137509962
Type: single nucleotide variant
Location: chr13:32339119 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1588: the 'interaction with rad51' region; the 'interaction with polh' region; the 'required for stimulation of polh dna polymerization activity' region

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA2 p.Ala1588Ser Uncertain significance ★★ ⚠ same residue
BRCA2 p.Ala1588Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 c.631+2T>G Pathogenic ★★★ same condition
BRCA2 c.8754+4A>G Pathogenic ★★★ same condition
BRCA2 c.8755-1G>A Pathogenic ★★★ same condition
BRCA2 p.Arg2520Ter Pathogenic ★★★ same condition
BRCA2 p.Arg3052Trp Pathogenic ★★★ same condition
BRCA2 p.Asn3124Ile 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-ala1588 (accessed [today's date]).

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