Is BAP1 p.Ser596Arg (c.1788C>G) pathogenic?

BAP1 p.Ser596Arg (c.1788C>G) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely benign (0.1951); Absent from gnomAD v4.1; Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Ser596Arg (c.1788C>G)?

BAP1 p.Ser596Arg (c.1788C>G) is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ser596Arg (c.1788C>G) in the general population?

BAP1 p.Ser596Arg (c.1788C>G) is absent from gnomAD v4.1 (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.Ser596Arg (c.1788C>G)?

AlphaMissense predicts likely benign (score 0.1951) — an in-silico prediction, not a clinical call.

BAP1 p.Ser596Arg

c.1788C>G · rs2153226488 · VCV2975840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.1951	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.82	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 2.9	GERP -0.27, phastCons 1
Overall
CADD	15.35	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BAP1
Protein: p.Ser596Arg
Coding: c.1788C>G
MANE Select: NM_004656
dbSNP: rs2153226488
Type: single nucleotide variant
Location: chr3:52403240 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 596: 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

BAP1-related tumor predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Ser596Gly Benign ★★ same residue
BAP1 p.Ser596fs Pathogenic ★★ same residue
BAP1 p.Ser596Lys Uncertain significance ★ same residue
BAP1 p.Ser596Thr Likely 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
BAP1 c.122+5G>A 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-ser596arg (accessed [today's date]).

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