Is BAP1 p.Ser63= (c.189T>C) pathogenic?

BAP1 p.Ser63= (c.189T>C) is classified Likely benign in BAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-31). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ser63= (c.189T>C)?

BAP1 p.Ser63= (c.189T>C) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ser63= (c.189T>C) in the general population?

BAP1 p.Ser63= (c.189T>C) is absent from gnomAD v4.1 (gnomAD).

BAP1 p.Ser63=

c.189T>C · rs1553646013 · VCV507806

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.7	GERP -0.36, phastCons 1
Overall
CADD	12.26	PHRED · no single calibrated threshold — expert panels disagree

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.Ser63=
Coding: c.189T>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1553646013
Type: single nucleotide variant
Location: chr3:52408540 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 63: the 'interaction with hip2' region; a β-strand

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

Also linked: BAP1-related tumor predisposition syndrome

Similar variants

BAP1 p.Ser63Cys Uncertain significance ★★ ⚠ same residue
BAP1 p.Ser63Phe Uncertain significance ★★ ⚠ same residue
BAP1 p.Ser63Pro Uncertain significance ★ ⚠ same residue
BAP1 p.Ser63fs 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-ser63 (accessed [today's date]).

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