Is FFAR3 p.Val50Ala (c.149T>C) pathogenic?

FFAR3 p.Val50Ala (c.149T>C) is classified Uncertain significance in FFAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1649); Very rare (popmax 0.00835%, amr).

How common is FFAR3 p.Val50Ala (c.149T>C) in the general population?

FFAR3 p.Val50Ala (c.149T>C) is very rare (popmax 0.00835%, amr) (gnomAD).

What do computational predictors say about FFAR3 p.Val50Ala (c.149T>C)?

AlphaMissense predicts likely benign (score 0.1649) — an in-silico prediction, not a clinical call.

FFAR3 p.Val50Ala

c.149T>C · VCV4024571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1649	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 193 bp · p 0.00082 · regional, not allelic
Overall
CADD	24.2	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 0.00835% Admixed American · 5/59,904 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000558% 9/1,611,662 alleles · very rare exomes 4/1,460,036 · genomes 5/151,626 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,981
European (non-Finnish)	0.000339%	294,601

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: FFAR3
Protein: p.Val50Ala
Coding: c.149T>C
MANE Select: NM_005304
Type: single nucleotide variant
Location: chr19:35359039 (GRCh38)
Gene constraint: LOEUF 1.874 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 2 PDB
Residue 50: an α-helix

Full FFAR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FFAR3 p.Ala256= Likely benign ★★ same type
FFAR3 p.Arg45His Benign ★★ same type
FFAR3 p.Met307Val Benign ★★ same type
FFAR3 p.Ser201= Likely benign ★★ same type
FFAR3 p.Ala103Thr Uncertain significance ★ ⚠ same type
FFAR3 p.Ala224Val Uncertain significance ★ ⚠ same type
FFAR3 p.Ala228Glu Uncertain significance ★ ⚠ same type
FFAR3 p.Ala285Asp 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/ffar3-p-val50ala (accessed [today's date]).

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