Is FFAR4 p.Arg148Pro (c.443G>C) pathogenic?

FFAR4 p.Arg148Pro (c.443G>C) is classified Uncertain significance in FFAR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely benign (0.0988); Very rare (popmax 0.0011%, sas).

How common is FFAR4 p.Arg148Pro (c.443G>C) in the general population?

FFAR4 p.Arg148Pro (c.443G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about FFAR4 p.Arg148Pro (c.443G>C)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

FFAR4 p.Arg148Pro

c.443G>C · VCV3850009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -7.19	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 1.3	GERP 4.7, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 21 kb · p 0.89 · regional, not allelic
Overall
CADD	9.524	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 0.0011% South Asian · 1/90,726 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00081% 13/1,604,550 alleles · very rare exomes 12/1,452,384 · genomes 1/152,166 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,726
European (non-Finnish)	0.00102%	98,214

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.Arg148Pro
Coding: c.443G>C
MANE Select: NM_001195755
Type: single nucleotide variant
Location: chr10:93567163 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 16 PDB
Residue 148: an α-helix

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

Similar variants

FFAR4 p.Arg148Gln Uncertain significance ★ ⚠ same residue
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

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-arg148pro (accessed [today's date]).

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