Is FFAR3 p.Pro255Leu (c.764C>T) pathogenic?

FFAR3 p.Pro255Leu (c.764C>T) is classified Uncertain significance in FFAR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.2696); Ultra-rare (popmax 0.0869%, eas).

How common is FFAR3 p.Pro255Leu (c.764C>T) in the general population?

FFAR3 p.Pro255Leu (c.764C>T) is ultra-rare (popmax 0.0869%, eas) (gnomAD).

What do computational predictors say about FFAR3 p.Pro255Leu (c.764C>T)?

AlphaMissense predicts likely benign (score 0.2696) — an in-silico prediction, not a clinical call.

FFAR3 p.Pro255Leu

c.764C>T · rs148946992 · VCV2561886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2696	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -13.17	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.75, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 192 bp · p 1.4e-08 · regional, not allelic
Overall
CADD	23.8	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 0.0869% East Asian · 39/44,892 alleles

Filtering AF 0.0652% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0577%

Overall 0.00489% 79/1,614,062 alleles · ultra-rare exomes 68/1,461,662 · genomes 11/152,400 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,151
Middle Eastern	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.0064%	15,624
African / African-American	0.00533%	18,768
South Asian	0.00329%	30,358
European (non-Finnish)	0.00229%	43,699

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.Pro255Leu
Coding: c.764C>T
MANE Select: NM_005304
dbSNP: rs148946992
Type: single nucleotide variant
Location: chr19:35359654 (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.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
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-pro255leu (accessed [today's date]).

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