Is BRCA2 p.Glu3002Lys (c.9004G>A) pathogenic?

BRCA2 p.Glu3002Lys (c.9004G>A) is classified Pathogenic/Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 27 submitters; last evaluated 2025-12-29). AlphaMissense: likely pathogenic (0.6004); Very rare (popmax 0.000255%, nfe); Associated with Autosomal dominant BRCA2-related cancer types.

What condition is associated with BRCA2 p.Glu3002Lys (c.9004G>A)?

BRCA2 p.Glu3002Lys (c.9004G>A) is associated with Autosomal dominant BRCA2-related cancer types, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Glu3002Lys (c.9004G>A) in the general population?

BRCA2 p.Glu3002Lys (c.9004G>A) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Glu3002Lys (c.9004G>A)?

AlphaMissense predicts likely pathogenic (score 0.6004) — an in-silico prediction, not a clinical call.

BRCA2 p.Glu3002Lys

c.9004G>A · rs80359152 · VCV38201

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 27 submitters

AlphaMissense

likely pathogenic

0.6004 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Autosomal dominant BRCA2-related cancer types

Computational evidence

Protein change
AlphaMissense	0.6004	likely pathogenic ✓ concordant with ClinVar · top 7% in BRCA2
REVEL	0.72	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	Δ0.56	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 0.00024 · regional, not allelic
Overall
CADD	32.0	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 0.000255% European (non-Finnish) · 3/1,178,456 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,084 alleles · very rare

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.Glu3002Lys
Coding: c.9004G>A
MANE Select: NM_000059
dbSNP: rs80359152
Type: single nucleotide variant
Location: chr13:32379800 (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

Autosomal dominant BRCA2-related cancer types

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

Similar variants

BRCA2 p.Glu3002Asp Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Glu3002Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Glu3002= Likely benign ★ 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
BRCA2 c.316+5G>C Pathogenic ★★★ same condition
BRCA2 c.475+1G>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-glu3002lys (accessed [today's date]).

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