Is BAP1 p.Gln436= (c.1308A>G) pathogenic?

BAP1 p.Gln436= (c.1308A>G) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0446%, eas); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Gln436= (c.1308A>G)?

BAP1 p.Gln436= (c.1308A>G) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Gln436= (c.1308A>G) in the general population?

BAP1 p.Gln436= (c.1308A>G) is ultra-rare (popmax 0.0446%, eas) (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.Gln436=

c.1308A>G · rs202038162 · VCV417291

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.33	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.12	GERP -4.2, phastCons 0.93
Overall
CADD	8.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0446% East Asian · 20/44,886 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00465% 75/1,614,100 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,244
Remaining individualsnot grpmax-eligible	0.024%	4,167
South Asian	0.022%	4,554
European (non-Finnish)	0.00161%	62,106
African / African-American	0.00133%	75,020

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.Gln436=
Coding: c.1308A>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs202038162
Type: single nucleotide variant
Location: chr3:52403837 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

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.Gln436Lys Uncertain significance ★★ ⚠ same residue
BAP1 p.Gln436Ter Pathogenic ★ same residue
BAP1 p.Gln436Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Gln436His Uncertain significance ★ ⚠ same residue
BAP1 p.Gln436fs Pathogenic 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-gln436 (accessed [today's date]).

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