Is BAP1 p.Tyr401Ter (c.1203T>G) pathogenic?

BAP1 p.Tyr401Ter (c.1203T>G) is classified Pathogenic in BAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-16). Ultra-rare (popmax 0.0384%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Tyr401Ter (c.1203T>G)?

BAP1 p.Tyr401Ter (c.1203T>G) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Tyr401Ter (c.1203T>G) in the general population?

BAP1 p.Tyr401Ter (c.1203T>G) is ultra-rare (popmax 0.0384%, amr) (gnomAD).

BAP1 p.Tyr401Ter

c.1203T>G · rs200156887 · VCV584647

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen); NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.38	GERP -2.5
Overall
CADD	29.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0384% Admixed American · 23/59,956 alleles

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

Overall 0.00613% 99/1,614,102 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%	6,945
South Asian	0.00988%	10,120
African / African-American	0.00799%	12,510
East Asian	0.00668%	14,961
European (non-Finnish)	0.00398%	25,107
Finnishnot grpmax-eligible	0.00156%	64,018

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.Tyr401Ter
Coding: c.1203T>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs200156887
Type: single nucleotide variant
Location: chr3:52404500 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Tyr401Asp Uncertain significance ★★ ⚠ same residue
BAP1 p.Tyr401Cys Uncertain significance ★★ ⚠ same residue
BAP1 p.Tyr401= Benign/Likely benign ★★ same residue
BAP1 p.Tyr401Phe Uncertain significance ★ ⚠ 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

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-tyr401ter (accessed [today's date]).

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