Is BAP1 p.Arg59Pro (c.176G>C) pathogenic?

BAP1 p.Arg59Pro (c.176G>C) is classified Pathogenic in BAP1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-05). AlphaMissense: likely pathogenic (0.9967); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with BAP1 p.Arg59Pro (c.176G>C)?

BAP1 p.Arg59Pro (c.176G>C) is associated with neurodevelopmental disorder (ClinVar).

How common is BAP1 p.Arg59Pro (c.176G>C) in the general population?

BAP1 p.Arg59Pro (c.176G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Arg59Pro (c.176G>C)?

AlphaMissense predicts likely pathogenic (score 0.9967) — an in-silico prediction, not a clinical call.

BAP1 p.Arg59Pro

c.176G>C · rs1298276806 · VCV1173080

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9967 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9967	likely pathogenic ✓ concordant with ClinVar
REVEL	0.516	indeterminate
SaProt	LLR -6.53	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	32.0	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.Arg59Pro
Coding: c.176G>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1298276806
Type: single nucleotide variant
Location: chr3:52408553 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 59: the 'interaction with hip2' region; a β-strand

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAP1 p.Arg59Trp Uncertain significance ★★ ⚠ same residue
BAP1 p.Arg59= Likely benign ★★ same residue
BAP1 p.Arg59Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Cys91Ser Pathogenic/Likely pathogenic ★★ same condition
BAP1 p.Arg718Gln Uncertain significance ★★ ⚠ same condition
BAP1 p.Arg59fs Pathogenic ★ same residue
BAP1 p.Leu49Pro Pathogenic ★ same condition
BAP1 p.Pro12Ala 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-arg59pro (accessed [today's date]).

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