Is BAP1 p.Ser105Thr (c.314G>C) pathogenic?

BAP1 p.Ser105Thr (c.314G>C) is classified Uncertain significance in BAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-12). AlphaMissense: likely benign (0.0864); Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BAP1 p.Ser105Thr (c.314G>C)?

BAP1 p.Ser105Thr (c.314G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BAP1 p.Ser105Thr (c.314G>C) in the general population?

BAP1 p.Ser105Thr (c.314G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BAP1 p.Ser105Thr (c.314G>C)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

BAP1 p.Ser105Thr

c.314G>C · rs1553645941 · VCV1728178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.08	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 -3.6	GERP -3.5
Overall
CADD	0.086	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,992 alleles

Overall 0.000137% 2/1,461,568 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,992
European (non-Finnish)	8.48e-05%	1,179,934

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.Ser105Thr
Coding: c.314G>C
MANE Select: NM_007212 · reported on NM_004656
dbSNP: rs1553645941
Type: single nucleotide variant
Location: chr3:52408019 (GRCh38)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 105: the 'interaction with hip2' region; an α-helix

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

Similar variants

BAP1 p.Ser105= Benign/Likely benign ★★ same residue
BAP1 p.Ser105Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BAP1 p.Ser105Asn Uncertain significance ★ ⚠ same residue
BAP1 p.Ser105Ile Uncertain significance ★ ⚠ 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.1251-1G>A 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-ser105thr (accessed [today's date]).

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