Is BAP1 p.Ser596Lys (c.1787_1788delinsAA) pathogenic?

BAP1 p.Ser596Lys (c.17871788delinsAA) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Ser596Lys (c.1787_1788delinsAA)?

BAP1 p.Ser596Lys (c.1787_1788delinsAA) is associated with BAP1-related tumor predisposition syndrome (ClinVar).

How is BAP1-related tumor predisposition syndrome inherited?

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

BAP1 p.Ser596Lys

c.1787_1788delinsAA · VCV4718635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

BAP1-related tumor predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP -0.27, phastCons 1

Variant & gene context

Gene: BAP1
Protein: p.Ser596Lys
Coding: c.1787_1788delinsAA
MANE Select: NM_004656
Type: Indel
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.Ser596fs Pathogenic ★★ same residue
BAP1 p.Ser596Gly Benign ★★ same residue
BAP1 p.Ser596Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Ser596Asn Uncertain significance ★ same residue
BAP1 p.Ala304Asn Uncertain significance ★★ same condition
BAP1 p.Ala378Leu Uncertain significance ★★ same condition
BAP1 p.Ala471Ile Uncertain significance ★★ same condition
BAP1 p.Glu198Leu Uncertain significance ★★ 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-ser596lys (accessed [today's date]).

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