Is CIDEA p.His98Arg (c.293A>G) pathogenic?

CIDEA p.His98Arg (c.293A>G) is classified Uncertain significance in CIDEA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.2442); Ultra-rare (popmax 0.0275%, nfe).

How common is CIDEA p.His98Arg (c.293A>G) in the general population?

CIDEA p.His98Arg (c.293A>G) is ultra-rare (popmax 0.0275%, nfe) (gnomAD).

What do computational predictors say about CIDEA p.His98Arg (c.293A>G)?

AlphaMissense predicts likely benign (score 0.2442) — an in-silico prediction, not a clinical call.

CIDEA p.His98Arg

c.293A>G · rs149990783 · VCV2454718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2442 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2442	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -12.89	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP -0.51, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 23 kb · p 0.35 · regional, not allelic
Overall
CADD	22.2	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 0.0275% European (non-Finnish) · 325/1,179,986 alleles

Filtering AF 0.025% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.021% 339/1,613,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0275%	3,631
Remaining individualsnot grpmax-eligible	0.016%	6,249
African / African-American	0.004%	24,974
Admixed American	0.00167%	59,992

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.His98Arg
Coding: c.293A>G
MANE Select: NM_001279
dbSNP: rs149990783
Type: single nucleotide variant
Location: chr18:12264416 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.69 · 1 PDB
Residue 98: the cide-n domain; a β-strand

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

Similar variants

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
CIDEA p.Arg197Gln 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-his98arg (accessed [today's date]).

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