Is BAP1 p.Gly178= (c.534C>T) pathogenic?

BAP1 p.Gly178= (c.534C>T) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-01). Rare (popmax 0.809%, eas); Associated with melanoma, uveal, susceptibility to, 2.

What condition is associated with BAP1 p.Gly178= (c.534C>T)?

BAP1 p.Gly178= (c.534C>T) is associated with melanoma, uveal, susceptibility to, 2, BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Gly178= (c.534C>T) in the general population?

BAP1 p.Gly178= (c.534C>T) is rare (popmax 0.809%, eas) (gnomAD).

BAP1 p.Gly178=

c.534C>T · rs200285587 · VCV240062

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.809%, eas)

Conditions

melanoma, uveal, susceptibility to, 2

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 -0.17	GERP -0.34, phastCons 0.097
Overall
CADD	17.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.809% East Asian · 363/44,880 alleles

Filtering AF 0.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.713%

Overall 0.0237% 383/1,614,182 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.809%	124
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.016%	6,251
Finnishnot grpmax-eligible	0.00625%	16,003
South Asian	0.0011%	91,082
European (non-Finnish)	0.000254%	393,349

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.Gly178=
Coding: c.534C>T
MANE Select: NM_004656
dbSNP: rs200285587
Type: single nucleotide variant
Location: chr3:52407220 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 178: the uch catalytic domain; a UniProt-annotated variant site (in a lung cancer sample; induces cytoplasmic accumulation; impairs deubiquitinase activity; up-regulates heat shock response; induces formation of beta-amyloid aggregates); a β-strand

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

Disease context

melanoma, uveal, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BAP1-related tumor predisposition syndrome hereditary neoplastic syndrome Kury-Isidor syndrome

Similar variants

BAP1 p.Gly178Asp Uncertain significance ★ ⚠ same residue
BAP1 p.Gly178Ser Uncertain significance ★ ⚠ 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-gly178 (accessed [today's date]).

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