Is GPBAR1 p.Pro142= (c.426C>T) pathogenic?

GPBAR1 p.Pro142= (c.426C>T) is classified Likely benign in GPBAR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-06-01). Rare (popmax 0.263%, mid); Associated with GPBAR1-related disorder.

What condition is associated with GPBAR1 p.Pro142= (c.426C>T)?

GPBAR1 p.Pro142= (c.426C>T) is associated with GPBAR1-related disorder (ClinVar).

How common is GPBAR1 p.Pro142= (c.426C>T) in the general population?

GPBAR1 p.Pro142= (c.426C>T) is rare (popmax 0.263%, mid) (gnomAD).

GPBAR1 p.Pro142=

c.426C>T · rs199613196 · VCV3054517

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.263%, mid)

Conditions

GPBAR1-related disorder

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 -12	GERP -5
Overall
CADD	0.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.263% Middle Eastern · 16/6,082 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.00472% 76/1,611,636 alleles · rare exomes 70/1,459,496 · genomes 6/152,140 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.263%	380
Remaining individualsnot grpmax-eligible	0.0128%	7,806
European (non-Finnish)	0.00432%	23,135
Admixed American	0.00167%	60,002

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.Pro142=
Coding: c.426C>T
MANE Select: NM_170699
dbSNP: rs199613196
Type: single nucleotide variant
Location: chr2:218263150 (GRCh38)
Gene constraint: LOEUF 1.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 5 PDB
Residue 142: 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.Pro142Leu 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-pro142 (accessed [today's date]).

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