Is GPBAR1 p.Ser98Pro (c.292T>C) pathogenic?

GPBAR1 p.Ser98Pro (c.292T>C) is classified Uncertain significance in GPBAR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-26). AlphaMissense: likely pathogenic (0.6524); Very rare (popmax 6.2e-05%); Associated with GPBAR1-related disorder.

What condition is associated with GPBAR1 p.Ser98Pro (c.292T>C)?

GPBAR1 p.Ser98Pro (c.292T>C) is associated with GPBAR1-related disorder (ClinVar).

How common is GPBAR1 p.Ser98Pro (c.292T>C) in the general population?

GPBAR1 p.Ser98Pro (c.292T>C) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about GPBAR1 p.Ser98Pro (c.292T>C)?

AlphaMissense predicts likely pathogenic (score 0.6524) — an in-silico prediction, not a clinical call.

GPBAR1 p.Ser98Pro

c.292T>C · VCV3354498

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6524 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GPBAR1-related disorder

Computational evidence

Protein change
AlphaMissense	0.6524	likely pathogenic
REVEL	0.682	pathogenic-leaning
SaProt	LLR -10.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 989 bp · p 0.066 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 6.2e-05%

Overall 6.2e-05% 1/1,613,778 alleles · very rare exomes 1/1,461,688 · genomes 0/152,090 · joint denominator

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: GPBAR1
Protein: p.Ser98Pro
Coding: c.292T>C
MANE Select: NM_170699
Type: single nucleotide variant
Location: chr2:218263016 (GRCh38)
Gene constraint: LOEUF 1.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 5 PDB
Residue 98: an α-helix

Full GPBAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GPBAR1-related disorder

Similar variants

GPBAR1 p.Ser98Phe Uncertain significance ★★ ⚠ same residue
GPBAR1 p.Ala113Val Uncertain significance ★★ ⚠ same condition
GPBAR1 p.Arg308Trp Uncertain significance ★★ ⚠ same condition
GPBAR1 p.Arg43His Uncertain significance ★★ ⚠ same condition
GPBAR1 p.Arg80Gln Uncertain significance ★★ ⚠ same condition
GPBAR1 p.Glu203Val Uncertain significance ★★ ⚠ same condition
GPBAR1 p.Tyr240Asp Uncertain significance ★★ ⚠ same condition
GPBAR1 p.Ala229Val Uncertain significance ★ ⚠ 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/gpbar1-p-ser98pro (accessed [today's date]).

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