Is GPR119 p.Ile10Phe (c.28A>T) pathogenic?

GPR119 p.Ile10Phe (c.28A>T) is classified Uncertain significance in GPR119 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.1018); Rare (popmax 0.122%, sas).

How common is GPR119 p.Ile10Phe (c.28A>T) in the general population?

GPR119 p.Ile10Phe (c.28A>T) is rare (popmax 0.122%, sas) (gnomAD).

What do computational predictors say about GPR119 p.Ile10Phe (c.28A>T)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

GPR119 p.Ile10Phe

c.28A>T · rs765822229 · VCV3101385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.122%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -6.18	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 2.7	GERP 0.66, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 1,004 bp · p 4.7e-05 · regional, not allelic
Overall
CADD	20.1	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 0.122% South Asian · 69/56,711 alleles

Filtering AF 0.0986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0902%

Overall 0.00656% 72/1,097,405 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.122%	822
Middle Eastern	0.0229%	4,365
Remaining individualsnot grpmax-eligible	0.0042%	23,784

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: GPR119
Protein: p.Ile10Phe
Coding: c.28A>T
MANE Select: NM_178471
dbSNP: rs765822229
Type: single nucleotide variant
Location: chrX:130385420 (GRCh38)
Structure: AlphaFold pLDDT 86.81 · 10 PDB
Residue 10: an α-helix

Full GPR119 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPR119 p.Leu236Val Likely benign ★★ same type
GPR119 p.Ser309Leu Benign ★★ same type
GPR119 p.Ala124Ser Uncertain significance ★ ⚠ same type
GPR119 p.Ala209Asp Uncertain significance ★ ⚠ same type
GPR119 p.Ala89Thr Uncertain significance ★ ⚠ same type
GPR119 p.Arg112His Uncertain significance ★ ⚠ same type
GPR119 p.Arg216Trp Uncertain significance ★ ⚠ same type
GPR119 p.Arg287Gln 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/gpr119-p-ile10phe (accessed [today's date]).

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