Is BAP1 p.Ala92Val (c.275C>T) pathogenic?

BAP1 p.Ala92Val (c.275C>T) is classified Pathogenic/Likely pathogenic in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-09). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1; Associated with Kury-Isidor syndrome.

What condition is associated with BAP1 p.Ala92Val (c.275C>T)?

BAP1 p.Ala92Val (c.275C>T) is associated with Kury-Isidor syndrome (ClinVar).

How common is BAP1 p.Ala92Val (c.275C>T) in the general population?

BAP1 p.Ala92Val (c.275C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Ala92Val (c.275C>T)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

BAP1 p.Ala92Val

c.275C>T · rs2153228142 · VCV2681785

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,516)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kury-Isidor syndrome

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar
REVEL	0.77	pathogenic-leaning
SaProt	LLR -13.91	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 12	GERP 1.8, phastCons 1
Overall
CADD	33.0	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

No allele count reported in gnomAD v4.1 (AN 1,610,516). 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.Ala92Val
Coding: c.275C>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2153228142
Type: single nucleotide variant
Location: chr3:52408058 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 92: the 'interaction with hip2' region

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

Similar variants

BAP1 p.Ala92Pro Uncertain significance ★★ ⚠ same residue
BAP1 p.Ala92= Likely benign ★ same residue
BAP1 p.Asn229Lys Likely pathogenic ★★ same condition
BAP1 p.Cys91Ser Pathogenic/Likely pathogenic ★★ same condition
BAP1 p.Gln392Ter Pathogenic ★★ same condition
BAP1 p.Trp202Ter Pathogenic ★★ same condition
BAP1 p.Tyr646Ter Pathogenic ★★ same condition
BAP1 p.Ala379Val Uncertain significance ★★ ⚠ 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-ala92val (accessed [today's date]).

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