Is FFAR3 p.Pro84Leu (c.251C>T) pathogenic?

FFAR3 p.Pro84Leu (c.251C>T) is classified Uncertain significance in FFAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: ambiguous (0.3788); Ultra-rare (popmax 0.0111%, nfe).

How common is FFAR3 p.Pro84Leu (c.251C>T) in the general population?

FFAR3 p.Pro84Leu (c.251C>T) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

What do computational predictors say about FFAR3 p.Pro84Leu (c.251C>T)?

AlphaMissense predicts ambiguous (score 0.3788) — an in-silico prediction, not a clinical call.

FFAR3 p.Pro84Leu

c.251C>T · rs764883825 · VCV2405756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3788	ambiguous
REVEL	0.264	benign-leaning
SaProt	LLR -11.00	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 0.69, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 359 bp · p 1.7e-22 · regional, not allelic
Overall
CADD	24.3	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 0.0111% European (non-Finnish) · 130/1,170,370 alleles

Filtering AF 0.00952% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00895%

Overall 0.00824% 132/1,602,168 alleles · ultra-rare exomes 120/1,451,416 · genomes 12/150,752 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0111%	9,003
Remaining individualsnot grpmax-eligible	0.00322%	31,029

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.Pro84Leu
Coding: c.251C>T
MANE Select: NM_005304
dbSNP: rs764883825
Type: single nucleotide variant
Location: chr19:35359141 (GRCh38)
Gene constraint: LOEUF 1.874 · pLI 0.31 (gnomAD)
Structure: AlphaFold pLDDT 86.90 · 2 PDB

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

Similar variants

FFAR3 p.Pro84Arg Uncertain significance ★ ⚠ same residue
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

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-pro84leu (accessed [today's date]).

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