Is BAP1 p.Cys91Arg (c.271T>C) pathogenic?

BAP1 p.Cys91Arg (c.271T>C) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-06-30). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Kury-Isidor syndrome.

What condition is associated with BAP1 p.Cys91Arg (c.271T>C)?

BAP1 p.Cys91Arg (c.271T>C) is associated with Kury-Isidor syndrome, BAP1-related tumor predisposition syndrome, neurodevelopmental disorder (ClinVar).

How common is BAP1 p.Cys91Arg (c.271T>C) in the general population?

BAP1 p.Cys91Arg (c.271T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Cys91Arg (c.271T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

BAP1 p.Cys91Arg

c.271T>C · rs1705222655 · VCV988095

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kury-Isidor syndrome

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 5% in BAP1
REVEL	0.984	strongly pathogenic-leaning
SaProt	LLR -14.25	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BAP1
Protein: p.Cys91Arg
Coding: c.271T>C
MANE Select: NM_004656
dbSNP: rs1705222655
Type: single nucleotide variant
Location: chr3:52408062 (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

Disease context

Kury-Isidor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome neurodevelopmental disorder

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.Cys91Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Cys91Trp Uncertain significance ★ ⚠ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A Pathogenic ★★ same condition
BAP1 c.122+1G>T 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-cys91arg (accessed [today's date]).

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