Is BAP1 p.Ala428fs (c.1282dup) pathogenic?

BAP1 p.Ala428fs (c.1282dup) is classified Pathogenic in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-11). Ultra-rare (gnomAD MAF 7.136e-07); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Ala428fs (c.1282dup)?

BAP1 p.Ala428fs (c.1282dup) is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ala428fs (c.1282dup) in the general population?

BAP1 p.Ala428fs (c.1282dup) is ultra-rare (gnomAD MAF 7.136e-07) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

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

BAP1 p.Ala428fs

c.1282dup · rs2471330374 · VCV2811159

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.136e-07)

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 haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 0.99, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: BAP1
Protein: p.Ala428fs
Coding: c.1282dup
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2471330374
Type: Duplication
Location: chr3:52403862 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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.Ala428Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Ala428Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Ala428Val Uncertain significance ★ ⚠ 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
BAP1 p.Glu198fs Pathogenic/Likely 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-ala428fs (accessed [today's date]).

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