Is BAP1 p.Leu96= (c.288G>A) pathogenic?

BAP1 p.Leu96= (c.288G>A) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.03%, eas); Associated with melanoma, uveal, susceptibility to, 2.

What condition is associated with BAP1 p.Leu96= (c.288G>A)?

BAP1 p.Leu96= (c.288G>A) is associated with melanoma, uveal, susceptibility to, 2, BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Leu96= (c.288G>A) in the general population?

BAP1 p.Leu96= (c.288G>A) is low-frequency (popmax 1.03%, eas) (gnomAD).

BAP1 p.Leu96=

c.288G>A · rs117382883 · VCV240057

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.03%, 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 3.9	GERP 1.8, phastCons 1
Overall
CADD	15.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.03% East Asian · 464/44,850 alleles

Filtering AF 0.957% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.926%

Overall 0.0365% 589/1,612,360 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.03%	97
South Asian	0.075%	1,333
Remaining individualsnot grpmax-eligible	0.0624%	1,602
European (non-Finnish)	0.00153%	65,512

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.Leu96=
Coding: c.288G>A
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs117382883
Type: single nucleotide variant
Location: chr3:52408045 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 96: the 'interaction with hip2' region; the 'interaction with nucleosomes via an acidic patch on histone h2a and histone h2b' region

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

Similar variants

BAP1 p.Leu96Ser Uncertain significance ★★ ⚠ same residue
BAP1 p.Leu96Trp 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-leu96 (accessed [today's date]).

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