Is BAP1 p.Tyr401Asp (c.1201T>G) pathogenic?

BAP1 p.Tyr401Asp (c.1201T>G) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-07). AlphaMissense: likely benign (0.1117); Ultra-rare (popmax 0.0384%, amr); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Tyr401Asp (c.1201T>G)?

BAP1 p.Tyr401Asp (c.1201T>G) is associated with BAP1-related tumor predisposition syndrome, Kury-Isidor syndrome (ClinVar).

How common is BAP1 p.Tyr401Asp (c.1201T>G) in the general population?

BAP1 p.Tyr401Asp (c.1201T>G) is ultra-rare (popmax 0.0384%, amr) (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.Tyr401Asp (c.1201T>G)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

BAP1 p.Tyr401Asp

c.1201T>G · rs376563004 · VCV584648

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -2.67	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 8	GERP 0.72, phastCons 1
Overall
CADD	19.13	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% Admixed American · 23/59,958 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00613% 99/1,614,108 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0384%	2,607
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0144%	6,944
South Asian	0.00988%	10,119
African / African-American	0.00799%	12,509
East Asian	0.00668%	14,964
European (non-Finnish)	0.00398%	25,107
Finnishnot grpmax-eligible	0.00156%	64,030

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.Tyr401Asp
Coding: c.1201T>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs376563004
Type: single nucleotide variant
Location: chr3:52404502 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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

Disease context

Also linked: Kury-Isidor syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Tyr401Ter Pathogenic ★★ same residue
BAP1 p.Tyr401Cys Uncertain significance ★★ ⚠ same residue
BAP1 p.Tyr401= Benign/Likely benign ★★ same residue
BAP1 p.Tyr401_Glu405delinsTer Pathogenic ★★ same residue
BAP1 p.Tyr401_Asp404del Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Tyr401_Asp408del Uncertain significance ★ same residue
BAP1 p.Tyr401Glu Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Tyr401Phe Uncertain significance ★ ⚠ same residue

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-tyr401asp (accessed [today's date]).

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