Is FFAR1 p.Phe117Val (c.349T>G) pathogenic?

FFAR1 p.Phe117Val (c.349T>G) is classified Uncertain significance in FFAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0937); Ultra-rare (popmax 0.0133%, amr).

How common is FFAR1 p.Phe117Val (c.349T>G) in the general population?

FFAR1 p.Phe117Val (c.349T>G) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about FFAR1 p.Phe117Val (c.349T>G)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

FFAR1 p.Phe117Val

c.349T>G · VCV4256961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -4.87	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 -1.8	GERP -3.7
Regional constraint	o/e 1.07	unconstrained · MANE · 899 bp · p 0.16 · regional, not allelic
Overall
CADD	0.415	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 0.0133% Admixed American · 8/60,008 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000496% 8/1,613,886 alleles · ultra-rare exomes 5/1,461,774 · genomes 3/152,112 · joint denominator

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: FFAR1
Protein: p.Phe117Val
Coding: c.349T>G
MANE Select: NM_005303
Type: single nucleotide variant
Location: chr19:35351900 (GRCh38)
Gene constraint: LOEUF 1.918 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 89.85 · 9 PDB
Residue 117: an α-helix

Full FFAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FFAR1 p.Ala116Thr Uncertain significance ★ ⚠ same type
FFAR1 p.Ala128Glu Uncertain significance ★ ⚠ same type
FFAR1 p.Ala173Thr Uncertain significance ★ ⚠ same type
FFAR1 p.Ala229Val Uncertain significance ★ ⚠ same type
FFAR1 p.Ala246Thr Uncertain significance ★ ⚠ same type
FFAR1 p.Ala246Val Uncertain significance ★ ⚠ same type
FFAR1 p.Ala30Thr Uncertain significance ★ ⚠ same type
FFAR1 p.Ala32Gly 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/ffar1-p-phe117val (accessed [today's date]).

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