Is FFAR2 p.Ala42Ser (c.124G>T) pathogenic?

FFAR2 p.Ala42Ser (c.124G>T) is classified Uncertain significance in FFAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-28). AlphaMissense: likely benign (0.1163); Ultra-rare (popmax 0.0267%, amr).

How common is FFAR2 p.Ala42Ser (c.124G>T) in the general population?

FFAR2 p.Ala42Ser (c.124G>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

What do computational predictors say about FFAR2 p.Ala42Ser (c.124G>T)?

AlphaMissense predicts likely benign (score 0.1163) — an in-silico prediction, not a clinical call.

FFAR2 p.Ala42Ser

c.124G>T · VCV3514784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1163 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1163	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -5.08	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 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 989 bp · p 0.7 · regional, not allelic
Overall
CADD	23.2	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 0.0267% Admixed American · 16/60,010 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00124% 20/1,613,764 alleles · ultra-rare exomes 17/1,461,538 · genomes 3/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,751
European (non-Finnish)	0.000339%	295,008

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.Ala42Ser
Coding: c.124G>T
MANE Select: NM_001370087
Type: single nucleotide variant
Location: chr19:35449838 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 12 PDB

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

Similar variants

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.Arg107Cys Uncertain significance ★ ⚠ same type
FFAR2 p.Arg107His Uncertain significance ★ ⚠ same type
FFAR2 p.Arg121Gly 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-ala42ser (accessed [today's date]).

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