Is BRCA2 p.His334= (c.1002T>C) pathogenic?

BRCA2 p.His334= (c.1002T>C) is classified Likely benign in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-27). Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with BRCA2 p.His334= (c.1002T>C)?

BRCA2 p.His334= (c.1002T>C) is associated with hereditary breast carcinoma, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.His334= (c.1002T>C) in the general population?

BRCA2 p.His334= (c.1002T>C) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

BRCA2 p.His334=

c.1002T>C · VCV3779419

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -0.16, phastCons 0.96
Overall
CADD	2.751	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.His334=
Coding: c.1002T>C
MANE Select: NM_000059
Type: single nucleotide variant
Location: chr13:32332480 (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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRCA2 p.His334Arg Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.His334Gln Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.His334fs Pathogenic ★★★ same residue
BRCA2 p.His334Asn Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.His334Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.His334Pro Uncertain significance ★ ⚠ same residue
BRCA2 p.His334Tyr Conflicting classifications of pathogenicity ★ 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-his334 (accessed [today's date]).

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