Is BAP1 p.Ser58= (c.174C>G) pathogenic?

BAP1 p.Ser58= (c.174C>G) is classified Benign/Likely benign in BAP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-10). Very rare (popmax 0.00102%, nfe); Associated with BAP1-related tumor predisposition syndrome.

What condition is associated with BAP1 p.Ser58= (c.174C>G)?

BAP1 p.Ser58= (c.174C>G) is associated with BAP1-related tumor predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Ser58= (c.174C>G) in the general population?

BAP1 p.Ser58= (c.174C>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is BAP1-related tumor predisposition syndrome inherited?

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

BAP1 p.Ser58=

c.174C>G · rs776102639 · VCV472677

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -3.1, phastCons 1
Overall
CADD	9.794	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,178,792 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.000823% 12/1,458,848 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.Ser58=
Coding: c.174C>G
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs776102639
Type: single nucleotide variant
Location: chr3:52408555 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 58: the 'interaction with hip2' region

Full BAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Also linked: hereditary neoplastic syndrome

For BAP1-related tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

BAP1 p.Ser58Ala Uncertain significance ★ ⚠ same residue
BAP1 p.Ser58Cys Uncertain significance ★ ⚠ same residue
BAP1 p.Ser58Phe Uncertain significance ★ ⚠ same residue
BAP1 p.Ser58Pro Uncertain significance ★ ⚠ same residue
BAP1 p.Ser58Tyr Uncertain significance ★ ⚠ same residue
BAP1 p.Ser58fs Pathogenic ★ same residue
BAP1 c.1117-1G>A Likely pathogenic ★★ same condition
BAP1 c.122+1G>A 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-ser58 (accessed [today's date]).

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