Is FFAR2 p.Cys198Ser (c.593G>C) pathogenic?

FFAR2 p.Cys198Ser (c.593G>C) is classified Uncertain significance in FFAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.6144); Absent from gnomAD v4.1.

How common is FFAR2 p.Cys198Ser (c.593G>C) in the general population?

FFAR2 p.Cys198Ser (c.593G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FFAR2 p.Cys198Ser (c.593G>C)?

AlphaMissense predicts likely pathogenic (score 0.6144) — an in-silico prediction, not a clinical call.

FFAR2 p.Cys198Ser

c.593G>C · VCV4256975

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6144 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6144	likely pathogenic
REVEL	0.501	indeterminate
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 989 bp · p 0.7 · regional, not allelic
Overall
CADD	28.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FFAR2
Protein: p.Cys198Ser
Coding: c.593G>C
MANE Select: NM_001370087
Type: single nucleotide variant
Location: chr19:35450307 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 12 PDB
Residue 198: an α-helix

Full FFAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FFAR2 p.Ala101Glu Uncertain significance ★ ⚠ same type
FFAR2 p.Ala101Pro Uncertain significance ★ ⚠ same type
FFAR2 p.Ala112Val Uncertain significance ★ ⚠ same type
FFAR2 p.Ala13Val Uncertain significance ★ ⚠ same type
FFAR2 p.Ala307Thr Uncertain significance ★ ⚠ same type
FFAR2 p.Ala42Ser Uncertain significance ★ ⚠ same type
FFAR2 p.Arg107Cys Uncertain significance ★ ⚠ same type
FFAR2 p.Arg107His 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/ffar2-p-cys198ser (accessed [today's date]).

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