Is BAP1 p.Thr64Ala (c.190A>G) pathogenic?

BAP1 p.Thr64Ala (c.190A>G) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-02-27). AlphaMissense: likely benign (0.0981); Very rare (popmax 0.00221%, sas); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Thr64Ala (c.190A>G)?

BAP1 p.Thr64Ala (c.190A>G) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Thr64Ala (c.190A>G) in the general population?

BAP1 p.Thr64Ala (c.190A>G) is very rare (popmax 0.00221%, sas) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BAP1 p.Thr64Ala (c.190A>G)?

AlphaMissense predicts likely benign (score 0.0981) — an in-silico prediction, not a clinical call.

BAP1 p.Thr64Ala

c.190A>G · rs1060503733 · VCV923904

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0981 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.0981	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1
Overall
CADD	24.8	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

Grpmax group 0.00221% South Asian · 2/90,480 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00031% 5/1,611,908 alleles · very rare exomes 4/1,459,714 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,240
European (non-Finnish)	0.000254%	393,065

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BAP1
Protein: p.Thr64Ala
Coding: c.190A>G
MANE Select: NM_004656
dbSNP: rs1060503733
Type: single nucleotide variant
Location: chr3:52408539 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 64: the uch catalytic domain

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

Disease context

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Thr64Ile Uncertain significance ★★ ⚠ same residue
BAP1 p.Thr64= Benign/Likely benign ★★ same residue
BAP1 p.Thr64Ser Uncertain significance ★ ⚠ same residue
BAP1 p.Thr64fs 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-thr64ala (accessed [today's date]).

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