Is CIDEA p.Arg197Gln (c.590G>A) pathogenic?

CIDEA p.Arg197Gln (c.590G>A) is classified Uncertain significance in CIDEA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0708); Ultra-rare (popmax 0.0626%, sas).

How common is CIDEA p.Arg197Gln (c.590G>A) in the general population?

CIDEA p.Arg197Gln (c.590G>A) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

What do computational predictors say about CIDEA p.Arg197Gln (c.590G>A)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

CIDEA p.Arg197Gln

c.590G>A · VCV4828765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -5.15	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 -0.05	GERP 0.53
Regional constraint	o/e 1.05	unconstrained · MANE · 23 kb · p 0.35 · regional, not allelic
Overall
CADD	3.216	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 0.0626% South Asian · 57/91,088 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00892% 144/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
European (non-Finnish)	0.00703%	14,218
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00167%	60,004

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: CIDEA
Protein: p.Arg197Gln
Coding: c.590G>A
MANE Select: NM_001279
Type: single nucleotide variant
Location: chr18:12277200 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.69 · 1 PDB

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

Similar variants

CIDEA p.Arg197Trp Uncertain significance ★ ⚠ same residue
CIDEA p.Ala127Gly Uncertain significance ★ ⚠ same type
CIDEA p.Ala181Asp Uncertain significance ★ ⚠ same type
CIDEA p.Ala181Val Uncertain significance ★ ⚠ same type
CIDEA p.Arg128Thr Uncertain significance ★ ⚠ same type
CIDEA p.Arg162Trp Uncertain significance ★ ⚠ same type
CIDEA p.Arg175Gln Uncertain significance ★ ⚠ same type
CIDEA p.Arg175Trp 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/cidea-p-arg197gln (accessed [today's date]).

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