Is FFAR2 p.Ile16Thr (c.47T>C) pathogenic?

FFAR2 p.Ile16Thr (c.47T>C) is classified Uncertain significance in FFAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely benign (0.2256); Ultra-rare (popmax 0.0252%, sas).

How common is FFAR2 p.Ile16Thr (c.47T>C) in the general population?

FFAR2 p.Ile16Thr (c.47T>C) is ultra-rare (popmax 0.0252%, sas) (gnomAD).

What do computational predictors say about FFAR2 p.Ile16Thr (c.47T>C)?

AlphaMissense predicts likely benign (score 0.2256) — an in-silico prediction, not a clinical call.

FFAR2 p.Ile16Thr

c.47T>C · rs767849907 · VCV2551105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2256 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0252%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2256	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.62	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 3.5	GERP 1.2, phastCons 0.83
Regional constraint	o/e 0.98	unconstrained · MANE · 989 bp · p 0.7 · regional, not allelic
Overall
CADD	19.4	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 0.0252% South Asian · 22/87,460 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0143%

Overall 0.00153% 22/1,440,938 alleles · ultra-rare

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: FFAR2
Protein: p.Ile16Thr
Coding: c.47T>C
MANE Select: NM_001370087
dbSNP: rs767849907
Type: single nucleotide variant
Location: chr19:35449761 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 12 PDB
Residue 16: an α-helix

Full FFAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FFAR2 p.Ile16Val Uncertain significance ★ ⚠ same residue
FFAR2 p.Ala101Glu Uncertain significance ★ ⚠ same type
FFAR2 p.Ala101Pro Uncertain significance ★ ⚠ same type
FFAR2 p.Ala112Val Uncertain significance ★ ⚠ same type
FFAR2 p.Ala13Val Uncertain significance ★ ⚠ same type
FFAR2 p.Ala307Thr Uncertain significance ★ ⚠ same type
FFAR2 p.Ala42Ser Uncertain significance ★ ⚠ same type
FFAR2 p.Arg107Cys 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/ffar2-p-ile16thr (accessed [today's date]).

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