Is FFAR3 p.Val149Met (c.445G>A) pathogenic?

FFAR3 p.Val149Met (c.445G>A) is classified Uncertain significance in FFAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.1424); Ultra-rare (popmax 0.0184%, amr).

How common is FFAR3 p.Val149Met (c.445G>A) in the general population?

FFAR3 p.Val149Met (c.445G>A) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

What do computational predictors say about FFAR3 p.Val149Met (c.445G>A)?

AlphaMissense predicts likely benign (score 0.1424) — an in-silico prediction, not a clinical call.

FFAR3 p.Val149Met

c.445G>A · rs530606489 · VCV2364720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1424 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1424	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -7.60	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 0.33	GERP -1.9, phastCons 0.006
Regional constraint	o/e 0.21	constrained · MANE · 359 bp · p 1.7e-22 · regional, not allelic
Overall
CADD	17.73	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 0.0184% Admixed American · 11/59,650 alleles

Filtering AF 0.0158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.0154% 247/1,606,020 alleles · ultra-rare exomes 222/1,453,736 · genomes 25/152,284 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0209%	4,781
Admixed Americangrpmax	0.0184%	5,423
European (non-Finnish)	0.0178%	5,617
Middle Eastern	0.0166%	6,036
African / African-American	0.008%	12,502
Finnishnot grpmax-eligible	0.00472%	21,179
East Asian	0.00446%	22,404
South Asian	0.00221%	45,294

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val149Met
Coding: c.445G>A
MANE Select: NM_005304
dbSNP: rs530606489
Type: single nucleotide variant
Location: chr19:35359335 (GRCh38)
Gene constraint: LOEUF 1.874 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 2 PDB
Residue 149: 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-val149met (accessed [today's date]).

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