Is BAP1 p.Pro12Thr (c.34C>A) pathogenic?

BAP1 p.Pro12Thr (c.34C>A) is classified Pathogenic in BAP1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2022-02-24). AlphaMissense: likely pathogenic (0.9986); Absent from gnomAD v4.1; Associated with Kury-Isidor syndrome.

What condition is associated with BAP1 p.Pro12Thr (c.34C>A)?

BAP1 p.Pro12Thr (c.34C>A) is associated with Kury-Isidor syndrome, neurodevelopmental disorder (ClinVar).

How common is BAP1 p.Pro12Thr (c.34C>A) in the general population?

BAP1 p.Pro12Thr (c.34C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Pro12Thr (c.34C>A)?

AlphaMissense predicts likely pathogenic (score 0.9986) — an in-silico prediction, not a clinical call.

BAP1 p.Pro12Thr

c.34C>A · rs2153228682 · VCV1064792

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9986 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,864)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Kury-Isidor syndrome

Computational evidence

Protein change
AlphaMissense	0.9986	likely pathogenic ✓ concordant with ClinVar
REVEL	0.834	moderately pathogenic-leaning
SaProt	LLR -13.82	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 1.6, phastCons 1
Overall
CADD	29.5	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 1,611,864). 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.Pro12Thr
Coding: c.34C>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs2153228682
Type: single nucleotide variant
Location: chr3:52409845 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 12: 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

Also linked: neurodevelopmental disorder

Similar variants

BAP1 p.Pro12Ala Likely pathogenic ★ same residue
BAP1 p.Pro12= Uncertain significance ★ same residue
BAP1 p.Pro12Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Ala92Val Pathogenic/Likely pathogenic ★★ same condition
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

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-pro12thr (accessed [today's date]).

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