Is BRCA2 p.Ala3345fs (c.10033dup) pathogenic?

BRCA2 p.Ala3345fs (c.10033dup) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-23). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ala3345fs (c.10033dup)?

BRCA2 p.Ala3345fs (c.10033dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ala3345fs (c.10033dup) in the general population?

BRCA2 p.Ala3345fs (c.10033dup) is no gnomAD frequency available for this variant (gnomAD).

BRCA2 p.Ala3345fs

c.10033dup · rs1234155856 · VCV1773772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 -1.1	GERP -4.7, phastCons 0.007

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.Ala3345fs
Coding: c.10033dup
MANE Select: NM_000059
dbSNP: rs1234155856
Type: Duplication
Location: chr13:32398545 (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

Similar variants

BRCA2 p.Ala3345Gly Uncertain significance ★★ same residue
BRCA2 p.Ala3345Ser Uncertain significance ★★ same residue
BRCA2 p.Ala3345Thr Uncertain significance ★★ same residue
BRCA2 p.Ala3345Val Uncertain significance ★★ ⚠ same residue
BRCA2 p.Ala3345= Likely benign ★★ same residue
BRCA2 p.Ala3345_Leu3346insTer Likely benign ★ same residue
BRCA2 p.Ala127fs Pathogenic ★★★ same condition
BRCA2 p.Ala2951fs 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-ala3345fs (accessed [today's date]).

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