Is BAP1 p.Ser104Arg (c.310A>C) pathogenic?

BAP1 p.Ser104Arg (c.310A>C) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). AlphaMissense: ambiguous (0.3945); Absent from gnomAD v4.1.

How common is BAP1 p.Ser104Arg (c.310A>C) in the general population?

BAP1 p.Ser104Arg (c.310A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BAP1 p.Ser104Arg (c.310A>C)?

AlphaMissense predicts ambiguous (score 0.3945) — an in-silico prediction, not a clinical call.

BAP1 p.Ser104Arg

c.310A>C · rs2153228112 · VCV1686754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3945	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -5.60	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Overall
CADD	24.5	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.Ser104Arg
Coding: c.310A>C
MANE Select: NM_004656
dbSNP: rs2153228112
Type: single nucleotide variant
Location: chr3:52408023 (GRCh38)
Gene constraint: LOEUF 0.324 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.87 · 4 PDB
Residue 104: the uch catalytic domain

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

Similar variants

BAP1 p.Ser104Asn Uncertain significance ★★ ⚠ same residue
BAP1 p.Ser104= Likely benign ★ 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
BAP1 c.122+5G>A Pathogenic/Likely pathogenic ★★ same type
BAP1 c.122+5G>C Likely pathogenic ★★ same type
BAP1 c.1251-1G>A 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-ser104arg (accessed [today's date]).

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