Is BAP1 c.*974C>T pathogenic?

BAP1 c.974C>T is classified Benign in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Common (popmax 5.78%, afr) — too common for a highly-penetrant pathogenic allele; Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 c.*974C>T?

BAP1 c.*974C>T is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How is BAP1-related tumor predisposition syndrome inherited?

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

BAP1 c.*974C>T

Q: How common is BAP1 c.*974C>T in the general population?

BAP1 c.*974C>T is common (popmax 5.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs9855479 · VCV346105

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.78%, afr) — too common for a highly-penetrant pathogenic allele

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 4.4	GERP -0.15, phastCons 1
Overall
CADD	16.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.78% African / African-American · 2,629/45,462 alleles

Filtering AF 5.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.52%

Overall 1.21% 2,814/233,480 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.78%	17
Remaining individualsnot grpmax-eligible	0.699%	143
Admixed American	0.624%	160
Middle Eastern	0.127%	788
South Asian	0.0362%	2,766
European (non-Finnish)	0.00763%	13,109

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
Coding: c.*974C>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs9855479
Type: single nucleotide variant
Location: chr3:52401314 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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

Disease context

BAP1-related tumor predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

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
BAP1 c.1251-1G>C Likely pathogenic ★★ same condition
BAP1 c.1251-2A>G 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-c-star-974c-t (accessed [today's date]).

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