Is BAP1 p.Arg59Gln (c.176G>A) pathogenic?

BAP1 p.Arg59Gln (c.176G>A) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-05). AlphaMissense: likely pathogenic (0.9899); Absent from gnomAD v4.1; Associated with Kury-Isidor syndrome.

What condition is associated with BAP1 p.Arg59Gln (c.176G>A)?

BAP1 p.Arg59Gln (c.176G>A) is associated with Kury-Isidor syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Arg59Gln (c.176G>A) in the general population?

BAP1 p.Arg59Gln (c.176G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Arg59Gln (c.176G>A)?

AlphaMissense predicts likely pathogenic (score 0.9899) — an in-silico prediction, not a clinical call.

BAP1 p.Arg59Gln

c.176G>A · rs1298276806 · VCV1320722

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9899 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Kury-Isidor syndrome

Computational evidence

Protein change
AlphaMissense	0.9899	likely pathogenic
REVEL	0.395	indeterminate
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	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

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.Arg59Gln
Coding: c.176G>A
MANE Select: NM_004656
dbSNP: rs1298276806
Type: single nucleotide variant
Location: chr3:52408553 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 59: the uch catalytic domain; 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

Similar variants

BAP1 p.Arg59Trp Uncertain significance ★★ ⚠ same residue
BAP1 p.Arg59= Likely benign ★★ same residue
BAP1 p.Arg59fs Pathogenic ★ same residue
BAP1 p.Arg59Pro Pathogenic ★ ⚠ 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
BAP1 c.122+5G>A 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-arg59gln (accessed [today's date]).

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