Is BAP1 p.Ser63Phe (c.188C>T) pathogenic?

BAP1 p.Ser63Phe (c.188C>T) is classified Uncertain significance in BAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-02). AlphaMissense: likely pathogenic (0.6555); Very rare (popmax 0.00221%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ser63Phe (c.188C>T)?

BAP1 p.Ser63Phe (c.188C>T) is associated with hereditary neoplastic syndrome, BAP1-related tumor predisposition syndrome (ClinVar).

How common is BAP1 p.Ser63Phe (c.188C>T) in the general population?

BAP1 p.Ser63Phe (c.188C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about BAP1 p.Ser63Phe (c.188C>T)?

AlphaMissense predicts likely pathogenic (score 0.6555) — an in-silico prediction, not a clinical call.

BAP1 p.Ser63Phe

c.188C>T · rs747311942 · VCV922270

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.6555	likely pathogenic
REVEL	0.108	moderately benign-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	27.6	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

Grpmax group 0.00221% South Asian · 2/90,460 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,459,620 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.Ser63Phe
Coding: c.188C>T
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs747311942
Type: single nucleotide variant
Location: chr3:52408541 (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.Ser63= Likely benign ★★ 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-ser63phe (accessed [today's date]).

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