Is BAP1 p.Ser596Thr (c.1787G>C) pathogenic?

BAP1 p.Ser596Thr (c.1787G>C) is classified Likely pathogenic in BAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-31). AlphaMissense: likely benign (0.0675); Absent from gnomAD v4.1; Associated with plasma cell myeloma.

What condition is associated with BAP1 p.Ser596Thr (c.1787G>C)?

BAP1 p.Ser596Thr (c.1787G>C) is associated with plasma cell myeloma (ClinVar).

How common is BAP1 p.Ser596Thr (c.1787G>C) in the general population?

BAP1 p.Ser596Thr (c.1787G>C) is absent from gnomAD v4.1 (gnomAD).

How is Multiple myeloma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BAP1 p.Ser596Thr (c.1787G>C)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

BAP1 p.Ser596Thr

c.1787G>C · rs1478603808 · VCV800323

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

plasma cell myeloma

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign ⚠ discordant with ClinVar
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.27	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 1.9	GERP -0.31, phastCons 0.98
Overall
CADD	12.48	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

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.Ser596Thr
Coding: c.1787G>C
MANE Select: NM_004656
dbSNP: rs1478603808
Type: single nucleotide variant
Location: chr3:52403241 (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

plasma cell myeloma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple myeloma (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

BAP1 p.Ser596Gly Benign ★★ same residue
BAP1 p.Ser596Arg Uncertain significance ★ ⚠ same residue
BAP1 p.Ser596fs Pathogenic ★★ same residue
BAP1 p.Ser596Asn Uncertain significance ★ same residue
BAP1 p.Ser596Lys Uncertain significance ★ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same type
BAP1 c.122+1G>A Pathogenic ★★ same type
BAP1 c.122+1G>T Pathogenic/Likely pathogenic ★★ same type

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-ser596thr (accessed [today's date]).

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