Is BAP1 p.Ser63fs (c.188_189del) pathogenic?

BAP1 p.Ser63fs (c.188189del) is classified Pathogenic in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ser63fs (c.188_189del)?

BAP1 p.Ser63fs (c.188_189del) is associated with hereditary neoplastic syndrome (ClinVar).

BAP1 p.Ser63fs

c.188_189del · VCV3260370

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: BAP1
Protein: p.Ser63fs
Coding: c.188_189del
MANE Select: NM_007212 · reported on NM_004656
Type: Microsatellite
Location: chr3:52408540 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 63: the 'interaction with hip2' region; a β-strand

Full BAP1 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

BAP1 p.Ser63Cys Uncertain significance ★★ ⚠ same residue
BAP1 p.Ser63Phe Uncertain significance ★★ ⚠ same residue
BAP1 p.Ser63= Likely benign ★★ same residue
BAP1 p.Ser63Pro Uncertain significance ★ ⚠ same residue
BAP1 p.Gln267fs Pathogenic ★★ same condition
BAP1 p.Glu611fs Pathogenic ★★ same condition
BAP1 p.His481fs Pathogenic ★★ same condition
BAP1 p.Ser492fs 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-ser63fs (accessed [today's date]).

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