Is BAP1 p.Val409fs (c.1155_1225dup) pathogenic?

BAP1 p.Val409fs (c.11551225dup) is classified Pathogenic in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-11). Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Val409fs (c.1155_1225dup)?

BAP1 p.Val409fs (c.1155_1225dup) is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How is BAP1-related tumor predisposition syndrome inherited?

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

BAP1 p.Val409fs

c.1155_1225dup · VCV4727816

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

BAP1-related tumor predisposition 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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.78, phastCons 0.27
Region caveats
Repeat context	tandem	CGTCATCCTCAT simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Variant & gene context

Gene: BAP1
Protein: p.Val409fs
Coding: c.1155_1225dup
MANE Select: NM_004656
Type: Duplication
Location: chr3:52404477 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 409: the 'disordered' region; a UniProt-annotated variant site (in tpds1)

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BAP1-related tumor predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Val409Gly Uncertain significance ★★ ⚠ same residue
BAP1 p.Val409Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Val409Met Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Val409= Likely benign ★ same residue
BAP1 p.Arg146fs Pathogenic ★★ same condition
BAP1 p.Asn504fs Pathogenic ★★ same condition
BAP1 p.Cys320fs Pathogenic ★★ same condition
BAP1 p.Gln280fs 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/bap1-p-val409fs (accessed [today's date]).

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