Is GPBAR1 p.Phe233= (c.699C>T) pathogenic?

GPBAR1 p.Phe233= (c.699C>T) is classified Uncertain significance in GPBAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-02-01). Ultra-rare (popmax 0.018%, mid).

How common is GPBAR1 p.Phe233= (c.699C>T) in the general population?

GPBAR1 p.Phe233= (c.699C>T) is ultra-rare (popmax 0.018%, mid) (gnomAD).

GPBAR1 p.Phe233=

c.699C>T · rs200077654 · VCV500237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, mid)

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 -4.6
Overall
CADD	0.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% Middle Eastern · 1/5,552 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00519%

Overall 0.00106% 17/1,602,484 alleles · ultra-rare exomes 13/1,450,308 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.018%	5,552
East Asian	0.0158%	6,341
South Asian	0.00112%	89,640
European (non-Finnish)	0.000681%	146,950

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.Phe233=
Coding: c.699C>T
MANE Select: NM_170699
dbSNP: rs200077654
Type: single nucleotide variant
Location: chr2:218263423 (GRCh38)
Gene constraint: LOEUF 1.572 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 5 PDB
Residue 233: an α-helix

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

Similar variants

GPBAR1 p.Ala113Val Uncertain significance ★★ ⚠ same type
GPBAR1 p.Ala213Thr Uncertain significance ★★ ⚠ same type
GPBAR1 p.Arg125Trp Uncertain significance ★★ ⚠ same type
GPBAR1 p.Arg187Cys Uncertain significance ★★ ⚠ same type
GPBAR1 p.Arg187His Uncertain significance ★★ ⚠ same type
GPBAR1 p.Arg308Trp Uncertain significance ★★ ⚠ same type
GPBAR1 p.Arg43His Uncertain significance ★★ ⚠ same type
GPBAR1 p.Arg80Gln Uncertain significance ★★ ⚠ 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/gpbar1-p-phe233 (accessed [today's date]).

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