Is BAP1 p.Thr111= (c.333C>T) pathogenic?

BAP1 p.Thr111= (c.333C>T) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-25). Ultra-rare (popmax 0.0128%, nfe); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Thr111= (c.333C>T)?

BAP1 p.Thr111= (c.333C>T) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Thr111= (c.333C>T) in the general population?

BAP1 p.Thr111= (c.333C>T) is ultra-rare (popmax 0.0128%, nfe) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

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

BAP1 p.Thr111=

c.333C>T · rs375700254 · VCV417279

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0128%, nfe)

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.54	GERP -1.8, phastCons 0.99
Overall
CADD	7.842	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0128% European (non-Finnish) · 151/1,180,002 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0105%

Overall 0.00985% 159/1,613,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0128%	7,815
Remaining individualsnot grpmax-eligible	0.0096%	10,412
Admixed American	0.00167%	59,992
African / African-American	0.00134%	74,876

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.Thr111=
Coding: c.333C>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs375700254
Type: single nucleotide variant
Location: chr3:52408000 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 111: the 'interaction with hip2' region; an α-helix

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.Thr111Ala Uncertain significance ★★ ⚠ same residue
BAP1 p.Thr111Ile Conflicting classifications of pathogenicity ★ ⚠ 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
BAP1 c.122+5G>C Likely pathogenic ★★ same condition
BAP1 c.1251-1G>A 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-thr111 (accessed [today's date]).

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