Is BAP1 p.Ala138fs (c.412_418del) pathogenic?

BAP1 p.Ala138fs (c.412418del) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-15). Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Ala138fs (c.412_418del)?

BAP1 p.Ala138fs (c.412_418del) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic 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.Ala138fs

c.412_418del · VCV4734228

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 6 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: BAP1
Protein: p.Ala138fs
Coding: c.412_418del
MANE Select: NM_004656
Type: Deletion
Location: chr3:52407418 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 138: the uch catalytic domain; an α-helix

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

Disease context

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Ala138Thr Uncertain significance ★ ⚠ same residue
BAP1 c.123-10_129del Likely pathogenic ★★ same condition
BAP1 c.1729+1del Pathogenic ★★ same condition
BAP1 c.1984-3_1999del Likely pathogenic ★★ same condition
BAP1 c.659+1del Likely pathogenic ★★ same condition
BAP1 p.Arg207fs Pathogenic ★★ same condition
BAP1 p.Arg518fs Pathogenic ★★ same condition
BAP1 p.Asn363fs 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-ala138fs (accessed [today's date]).

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