Is FFAR3 p.Arg45His (c.134G>A) pathogenic?

FFAR3 p.Arg45His (c.134G>A) is classified Benign in FFAR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-06-22). AlphaMissense: likely benign (0.0797); Common (popmax 27.9%, mid) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about FFAR3 p.Arg45His (c.134G>A)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

FFAR3 p.Arg45His

Q: How common is FFAR3 p.Arg45His (c.134G>A) in the general population?

FFAR3 p.Arg45His (c.134G>A) is common (popmax 27.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.134G>A · rs62109581 · VCV768984

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 27.9%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.25	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 0.35	GERP -1.6, phastCons 0.007
Regional constraint	o/e 0.63	unconstrained · MANE · 193 bp · p 0.00082 · regional, not allelic
Overall
CADD	17.03	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.9% Middle Eastern · 1,651/5,924 alleles

Filtering AF 26.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.3%

Overall 21.6% 342,827/1,585,386 alleles · common exomes 314,279/1,437,960 · genomes 28,548/147,426 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	27.9%	4
Amishnot grpmax-eligible	25.8%	4
Ashkenazi Jewishnot grpmax-eligible	25.3%	4
East Asian	25%	4
Finnishnot grpmax-eligible	23.8%	4
European (non-Finnish)	22%	5
Remaining individualsnot grpmax-eligible	21.8%	5
South Asian	21.5%	5
Admixed American	18.6%	5
African / African-American	12.3%	8

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.Arg45His
Coding: c.134G>A
MANE Select: NM_005304
dbSNP: rs62109581
Type: single nucleotide variant
Location: chr19:35359024 (GRCh38)
Gene constraint: LOEUF 1.874 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 2 PDB
Residue 45: a UniProt-annotated variant site (in); 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.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
FFAR3 p.Ala320Val 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-arg45his (accessed [today's date]).

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