Is FFAR2 p.Ile46Val (c.136A>G) pathogenic?

FFAR2 p.Ile46Val (c.136A>G) is classified Benign in FFAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-12). AlphaMissense: likely benign (0.1368); Low-frequency (popmax 2.87%, afr).

How common is FFAR2 p.Ile46Val (c.136A>G) in the general population?

FFAR2 p.Ile46Val (c.136A>G) is low-frequency (popmax 2.87%, afr) (gnomAD).

What do computational predictors say about FFAR2 p.Ile46Val (c.136A>G)?

AlphaMissense predicts likely benign (score 0.1368) — an in-silico prediction, not a clinical call.

FFAR2 p.Ile46Val

c.136A>G · rs73931123 · VCV791358

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1368 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.87%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1368	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -6.52	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 1.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 989 bp · p 0.7 · regional, not allelic
Overall
CADD	19.87	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.87% African / African-American · 2,155/75,060 alleles

Filtering AF 2.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.73%

Overall 0.146% 2,356/1,613,832 alleles · low-frequency exomes 1,170/1,461,520 · genomes 1,186/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.87%	35
Middle Eastern	0.165%	606
Admixed American	0.143%	698
Remaining individualsnot grpmax-eligible	0.134%	744
South Asian	0.00329%	30,359
European (non-Finnish)	0.00153%	65,557

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.Ile46Val
Coding: c.136A>G
MANE Select: NM_001370087
dbSNP: rs73931123
Type: single nucleotide variant
Location: chr19:35449850 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 12 PDB
Residue 46: an α-helix

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

Similar variants

FFAR2 p.Ile46Thr 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-ile46val (accessed [today's date]).

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