Is FFAR4 p.Phe115Val (c.343T>G) pathogenic?

FFAR4 p.Phe115Val (c.343T>G) is classified Uncertain significance in FFAR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: likely pathogenic (0.5772); Ultra-rare (popmax 0.0217%, amr).

How common is FFAR4 p.Phe115Val (c.343T>G) in the general population?

FFAR4 p.Phe115Val (c.343T>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about FFAR4 p.Phe115Val (c.343T>G)?

AlphaMissense predicts likely pathogenic (score 0.5772) — an in-silico prediction, not a clinical call.

FFAR4 p.Phe115Val

c.343T>G · VCV3850010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5772 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5772	likely pathogenic
REVEL	0.108	moderately benign-leaning
SaProt	LLR -8.56	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 5.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 21 kb · p 0.89 · regional, not allelic
Overall
CADD	21.5	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 0.0217% Admixed American · 13/59,952 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000807% 13/1,611,354 alleles · ultra-rare exomes 12/1,459,154 · genomes 1/152,200 · 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.Phe115Val
Coding: c.343T>G
MANE Select: NM_001195755
Type: single nucleotide variant
Location: chr10:93567063 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.16 · 16 PDB
Residue 115: 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-phe115val (accessed [today's date]).

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