Is BRCA2 p.Leu3382fs (c.10145_10146del) pathogenic?

BRCA2 p.Leu3382fs (c.1014510146del) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-09). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Leu3382fs (c.10145_10146del)?

BRCA2 p.Leu3382fs (c.10145_10146del) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Leu3382fs (c.10145_10146del) in the general population?

BRCA2 p.Leu3382fs (c.10145_10146del) is absent from gnomAD (gnomAD).

BRCA2 p.Leu3382fs

c.10145_10146del · rs2137667100 · VCV1095582

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic 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	escapes	premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.48	GERP -0.15

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Leu3382fs
Coding: c.10145_10146del
MANE Select: NM_000059
dbSNP: rs2137667100
Type: Deletion
Location: chr13:32398658 (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 neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA2 p.Leu3382= Likely benign ★ same residue
BRCA2 c.5217_5224del Pathogenic ★★★ same condition
BRCA2 c.68-?_316+?del Pathogenic ★★★ same condition
BRCA2 c.8312del Pathogenic ★★★ same condition
BRCA2 c.8633-24_8634del Pathogenic ★★★ same condition
BRCA2 c.8756del Pathogenic ★★★ same condition
BRCA2 c.9403del Pathogenic ★★★ same condition
BRCA2 p.Ala1109fs 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-leu3382fs (accessed [today's date]).

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