Is BAP1 p.Glu602Asp (c.1806G>C) pathogenic?

BAP1 p.Glu602Asp (c.1806G>C) is classified Conflicting classifications of pathogenicity in BAP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.0718); Very rare (popmax 0.0089%, nfe); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Glu602Asp (c.1806G>C)?

BAP1 p.Glu602Asp (c.1806G>C) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Glu602Asp (c.1806G>C) in the general population?

BAP1 p.Glu602Asp (c.1806G>C) is very rare (popmax 0.0089%, nfe) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

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

What do computational predictors say about BAP1 p.Glu602Asp (c.1806G>C)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

BAP1 p.Glu602Asp

c.1806G>C · rs759423683 · VCV472679

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0089%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -1.5, phastCons 0.006
Overall
CADD	13.72	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0089% European (non-Finnish) · 105/1,180,054 alleles

Filtering AF 0.00749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00651% 105/1,614,096 alleles · very rare

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.Glu602Asp
Coding: c.1806G>C
MANE Select: NM_004656
dbSNP: rs759423683
Type: single nucleotide variant
Location: chr3:52403222 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 602: a UniProt-annotated variant site (in tpds1); the 'disordered' region; the 'interaction with brca1' 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.Glu602Gln Uncertain significance ★★ ⚠ same residue
BAP1 p.Glu602Gly Uncertain significance ★★ ⚠ same residue
BAP1 p.Glu602= Benign/Likely benign ★★ same residue
BAP1 p.Glu602del Conflicting classifications of pathogenicity ★ same residue
BAP1 p.Glu602Val 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

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-glu602asp (accessed [today's date]).

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