Is BAP1 p.Cys91fs (c.272dup) pathogenic?

BAP1 p.Cys91fs (c.272dup) is classified Likely pathogenic in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-27). No gnomAD frequency available for this variant.

How common is BAP1 p.Cys91fs (c.272dup) in the general population?

BAP1 p.Cys91fs (c.272dup) is no gnomAD frequency available for this variant (gnomAD).

BAP1 p.Cys91fs

c.272dup · rs2153228146 · VCV1338577

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 5 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.56	GERP -2.5, phastCons 0.87

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: BAP1
Protein: p.Cys91fs
Coding: c.272dup
MANE Select: NM_004656
dbSNP: rs2153228146
Type: Duplication
Location: chr3:52408060 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 91: the uch catalytic domain; an active site; a UniProt-annotated variant site (in kuris); a UniProt-annotated variant site (in kuris; loss-of-function variant; unable to rescue impaired h2ak119ub deubiquitination when expressed in bap1-deficient cells; does not affect localization to the nucleus); a UniProt-annotated variant site (in kuris; loss-of-function variant; increased steady-state level of ubiquitinated h2a are found in patient cells; unable to rescue impaired h2ak119ub deubiquitination when expressed in bap1-deficient cells; abolishes deubiquitinase activity; does not affect its ability to interfere with brca1 e3 ligase activity; does not affect localization to the nucleus; has a dominant negative effect on cell growth; does not affect interaction with foxk1 and foxk2; has no effect on pr-dub complex assembly; unable to activate transcription); a UniProt-annotated variant site (found in a malignant pleural mesothelioma sample); an α-helix

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

Similar variants

BAP1 p.Cys91Ser Pathogenic/Likely pathogenic ★★ same residue
BAP1 p.Cys91Tyr Uncertain significance ★★ ⚠ same residue
BAP1 p.Cys91Ter Likely pathogenic ★ same residue
BAP1 p.Cys91Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Cys91Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Cys91Trp Uncertain significance ★ ⚠ same residue
BAP1 p.Arg146fs Pathogenic ★★ same type
BAP1 p.Asn504fs Pathogenic ★★ same type

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-cys91fs (accessed [today's date]).

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