Is FFAR4 p.Pro300Ser (c.898C>T) pathogenic?

FFAR4 p.Pro300Ser (c.898C>T) is classified Uncertain significance in FFAR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.3348); Very rare (popmax 0.0011%, sas).

How common is FFAR4 p.Pro300Ser (c.898C>T) in the general population?

FFAR4 p.Pro300Ser (c.898C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about FFAR4 p.Pro300Ser (c.898C>T)?

AlphaMissense predicts likely benign (score 0.3348) — an in-silico prediction, not a clinical call.

FFAR4 p.Pro300Ser

c.898C>T · rs2494047426 · VCV2492845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3348	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 21 kb · p 0.89 · regional, not allelic
Overall
CADD	21.2	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 · 1/91,058 alleles

Overall 6.2e-05% 1/1,614,104 alleles · very rare exomes 1/1,461,876 · genomes 0/152,228 · joint denominator

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.Pro300Ser
Coding: c.898C>T
MANE Select: NM_001195755
dbSNP: rs2494047426
Type: single nucleotide variant
Location: chr10:93587421 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 16 PDB
Residue 300: an α-helix

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

Similar variants

FFAR4 p.Pro300Leu 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-pro300ser (accessed [today's date]).

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