Is CAD p.Arg1789Gln (c.5366G>A) pathogenic?

CAD p.Arg1789Gln (c.5366G>A) is classified Conflicting classifications of pathogenicity in CAD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-13). AlphaMissense: ambiguous (0.5087); Very rare (popmax 0.00223%, eas); Associated with infantile epileptic-dyskinetic encephalopathy.

What condition is associated with CAD p.Arg1789Gln (c.5366G>A)?

CAD p.Arg1789Gln (c.5366G>A) is associated with infantile epileptic-dyskinetic encephalopathy (ClinVar).

How common is CAD p.Arg1789Gln (c.5366G>A) in the general population?

CAD p.Arg1789Gln (c.5366G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Infantile epileptic-dyskinetic encephalopathy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CAD p.Arg1789Gln (c.5366G>A)?

AlphaMissense predicts ambiguous (score 0.5087) — an in-silico prediction, not a clinical call.

CAD p.Arg1789Gln

c.5366G>A · rs1341652994 · VCV2151926

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

infantile epileptic-dyskinetic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.5087	ambiguous
REVEL	0.721	pathogenic-leaning
SaProt	LLR -6.70	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,919 bp · p 0.1 · regional, not allelic
Overall
CADD	29.7	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 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000479% 7/1,461,602 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000424%	235,974

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: CAD
Protein: p.Arg1789Gln
Coding: c.5366G>A
MANE Select: NM_004341
dbSNP: rs1341652994
Type: single nucleotide variant
Location: chr2:27239443 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1789: a UniProt-annotated variant site (in dee50; uncertain significance); the 'linker' region

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

Disease context

infantile epileptic-dyskinetic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile epileptic-dyskinetic encephalopathy (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy, Neonatal

Similar variants

CAD p.Arg1789Ter Pathogenic ★★ same residue
CAD p.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CAD p.Arg1722Trp Likely pathogenic ★ ⚠ same condition
CAD p.Arg1475Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CAD p.Gly526Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
CAD p.His1687Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
CAD p.Phe1199fs Pathogenic ★ same condition
CAD p.Thr793fs Likely pathogenic ★ same condition

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/cad-p-arg1789gln (accessed [today's date]).

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