Is BAP1 p.Thr524= (c.1572C>T) pathogenic?

BAP1 p.Thr524= (c.1572C>T) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-17). Absent from gnomAD v4.1; Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Thr524= (c.1572C>T)?

BAP1 p.Thr524= (c.1572C>T) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Thr524= (c.1572C>T) in the general population?

BAP1 p.Thr524= (c.1572C>T) is absent from gnomAD v4.1 (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.Thr524=

c.1572C>T · rs1705042850 · VCV1119376

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.2	GERP -1.6, phastCons 1
Overall
CADD	14.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BAP1
Protein: p.Thr524=
Coding: c.1572C>T
MANE Select: NM_004656
dbSNP: rs1705042850
Type: single nucleotide variant
Location: chr3:52403573 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 524: a UniProt-annotated variant site (in tpds1); the 'disordered' region

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.Thr524Asn Uncertain significance ★★ ⚠ same residue
BAP1 p.Thr524Ile Uncertain significance ★★ ⚠ same residue
BAP1 p.Thr524Pro Uncertain significance ★★ ⚠ same residue
BAP1 p.Thr524Ala Uncertain significance ★ ⚠ same residue
BAP1 p.Thr524Ser Benign ★ 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

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-thr524 (accessed [today's date]).

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