Is FFAR4 p.Val65Ala (c.194T>C) pathogenic?

FFAR4 p.Val65Ala (c.194T>C) is classified Uncertain significance in FFAR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1819); Ultra-rare (popmax 0.0252%, amr).

How common is FFAR4 p.Val65Ala (c.194T>C) in the general population?

FFAR4 p.Val65Ala (c.194T>C) is ultra-rare (popmax 0.0252%, amr) (gnomAD).

What do computational predictors say about FFAR4 p.Val65Ala (c.194T>C)?

AlphaMissense predicts likely benign (score 0.1819) — an in-silico prediction, not a clinical call.

FFAR4 p.Val65Ala

c.194T>C · rs143911724 · VCV3094574

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1819 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0252%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1819	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.31	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 7.5	GERP 6.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 21 kb · p 0.89 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0252% Admixed American · 15/59,628 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0125%

Overall 0.00149% 24/1,608,976 alleles · ultra-rare exomes 10/1,456,752 · genomes 14/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0252%	3,975
Remaining individualsnot grpmax-eligible	0.00802%	12,466
African / African-American	0.004%	24,970
South Asian	0.0011%	90,574

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: FFAR4
Protein: p.Val65Ala
Coding: c.194T>C
MANE Select: NM_001195755
dbSNP: rs143911724
Type: single nucleotide variant
Location: chr10:93566914 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 16 PDB
Residue 65: an α-helix

Full FFAR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RBP4 p.Gly93Asp Likely pathogenic ★★ same type
FFAR4 c.696+2944C>T Uncertain significance ★ same type
FFAR4 c.696+2949C>T Uncertain significance ★ same type
FFAR4 c.696+2974T>C Uncertain significance ★ same type
FFAR4 p.Ala131Val Uncertain significance ★ ⚠ same type
FFAR4 p.Ala160Ser Uncertain significance ★ ⚠ same type
FFAR4 p.Ala167Val Uncertain significance ★ ⚠ same type
FFAR4 p.Ala315Thr 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/ffar4-p-val65ala (accessed [today's date]).

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