Is FFAR3 p.Met307Val (c.919A>G) pathogenic?

FFAR3 p.Met307Val (c.919A>G) is classified Benign in FFAR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-06-22). AlphaMissense: likely benign (0.0532); Common (popmax 9.75%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about FFAR3 p.Met307Val (c.919A>G)?

AlphaMissense predicts likely benign (score 0.0532) — an in-silico prediction, not a clinical call.

FFAR3 p.Met307Val

Q: How common is FFAR3 p.Met307Val (c.919A>G) in the general population?

FFAR3 p.Met307Val (c.919A>G) is common (popmax 9.75%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.919A>G · rs150331058 · VCV771218

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0532 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.75%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0532	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -5.52	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 -11	GERP -3
Regional constraint	o/e 0.15	constrained · MANE · 223 bp · p 8.3e-16 · regional, not allelic
Overall
CADD	0.002	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 9.75% African / African-American · 6,164/63,244 alleles

Filtering AF 9.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.46%

Overall 2.22% 33,056/1,487,748 alleles · common exomes 29,346/1,354,010 · genomes 3,710/133,738 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.75%	10
Remaining individualsnot grpmax-eligible	2.24%	45
European (non-Finnish)	2.1%	48
Finnishnot grpmax-eligible	1.74%	58
Middle Eastern	1.62%	62
Admixed American	1.17%	85
Ashkenazi Jewishnot grpmax-eligible	1.15%	87
South Asian	0.716%	140
Amishnot grpmax-eligible	0.122%	822
East Asian	0.0582%	1,718

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.Met307Val
Coding: c.919A>G
MANE Select: NM_005304
dbSNP: rs150331058
Type: single nucleotide variant
Location: chr19:35359809 (GRCh38)
Gene constraint: LOEUF 1.874 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 2 PDB
Residue 307: the 'disordered' region

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

Similar variants

FFAR3 p.Met307Leu Uncertain significance ★ ⚠ same residue
FFAR3 p.Ala256= Likely benign ★★ same type
FFAR3 p.Arg45His 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-met307val (accessed [today's date]).

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