Is FFAR2 p.Arg107His (c.320G>A) pathogenic?

FFAR2 p.Arg107His (c.320G>A) is classified Uncertain significance in FFAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely pathogenic (0.6966); Very rare (popmax 0.0022%, sas).

How common is FFAR2 p.Arg107His (c.320G>A) in the general population?

FFAR2 p.Arg107His (c.320G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about FFAR2 p.Arg107His (c.320G>A)?

AlphaMissense predicts likely pathogenic (score 0.6966) — an in-silico prediction, not a clinical call.

FFAR2 p.Arg107His

c.320G>A · rs758560714 · VCV2561289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6966 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6966	likely pathogenic
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -12.01	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 989 bp · p 0.7 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.00105% 17/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,918
European (non-Finnish)	0.00102%	98,336

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.Arg107His
Coding: c.320G>A
MANE Select: NM_001370087
dbSNP: rs758560714
Type: single nucleotide variant
Location: chr19:35450034 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 12 PDB
Residue 107: an α-helix

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

Similar variants

FFAR2 p.Arg107Cys 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.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-arg107his (accessed [today's date]).

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