Is BAP1 p.Val603Leu (c.1807G>C) pathogenic?

BAP1 p.Val603Leu (c.1807G>C) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-04). AlphaMissense: likely benign (0.0894); Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Val603Leu (c.1807G>C)?

BAP1 p.Val603Leu (c.1807G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Val603Leu (c.1807G>C) in the general population?

BAP1 p.Val603Leu (c.1807G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BAP1 p.Val603Leu (c.1807G>C)?

AlphaMissense predicts likely benign (score 0.0894) — an in-silico prediction, not a clinical call.

BAP1 p.Val603Leu

c.1807G>C · rs1329653090 · VCV1780502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0894 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0894	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -7.02	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 0.77	GERP -0.25, phastCons 0.003
Overall
CADD	15.19	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,848 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.Val603Leu
Coding: c.1807G>C
MANE Select: NM_004656
dbSNP: rs1329653090
Type: single nucleotide variant
Location: chr3:52403221 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 603: 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAP1 p.Val603= Benign/Likely benign ★★ same residue
BAP1 p.Val603Ala Uncertain significance ★ ⚠ same residue
BAP1 p.Val603Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Val603Phe 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.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-val603leu (accessed [today's date]).

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