Is BAP1 p.Asn229Lys (c.687C>A) pathogenic?

BAP1 p.Asn229Lys (c.687C>A) is classified Likely pathogenic in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-11). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Kury-Isidor syndrome.

What condition is associated with BAP1 p.Asn229Lys (c.687C>A)?

BAP1 p.Asn229Lys (c.687C>A) is associated with Kury-Isidor syndrome (ClinVar).

How common is BAP1 p.Asn229Lys (c.687C>A) in the general population?

BAP1 p.Asn229Lys (c.687C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Asn229Lys (c.687C>A)?

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

BAP1 p.Asn229Lys

c.687C>A · rs2153227484 · VCV2429331

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Kury-Isidor syndrome

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar
REVEL	0.457	indeterminate
SaProt	LLR -15.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.9	GERP 2.1, 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.Asn229Lys
Coding: c.687C>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2153227484
Type: single nucleotide variant
Location: chr3:52406349 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 229: a β-strand

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.Asn229His Likely pathogenic ★ same residue
BAP1 p.Asn229Ser Uncertain significance ★ ⚠ same residue
BAP1 p.Asn229= Likely benign ★ same residue
BAP1 p.Ala92Val Pathogenic/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

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-asn229lys (accessed [today's date]).

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