Is BRCA2 p.Glu1441fs (c.4320del) pathogenic?

BRCA2 p.Glu1441fs (c.4320del) is classified Pathogenic in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Glu1441fs (c.4320del)?

BRCA2 p.Glu1441fs (c.4320del) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

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

BRCA2 p.Glu1441fs

c.4320del · VCV3663151

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.1	GERP -4.6, phastCons 0.001

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: BRCA2
Protein: p.Glu1441fs
Coding: c.4320del
MANE Select: NM_000059
Type: Deletion
Location: chr13:32338673 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1441: 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

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

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Glu1441= Likely benign ★★★ same residue
BRCA2 p.Glu1441Ter Pathogenic/Likely pathogenic ★★ same residue
BRCA2 p.Glu1441Ala Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Glu1441Gln Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Glu1441Gly Uncertain significance ★ same residue
BRCA2 p.Glu1441Lys Conflicting classifications of pathogenicity ★ same residue
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del 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-glu1441fs (accessed [today's date]).

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