Is CAD p.Phe1199fs (c.3596del) pathogenic?

CAD p.Phe1199fs (c.3596del) is classified Pathogenic in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-17). Associated with infantile epileptic-dyskinetic encephalopathy.

What condition is associated with CAD p.Phe1199fs (c.3596del)?

CAD p.Phe1199fs (c.3596del) is associated with infantile epileptic-dyskinetic encephalopathy (ClinVar).

How is Infantile epileptic-dyskinetic encephalopathy inherited?

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

CAD p.Phe1199fs

c.3596del · VCV4848445

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

infantile epileptic-dyskinetic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 22 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -0.71, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CAD
Protein: p.Phe1199fs
Coding: c.3596del
MANE Select: NM_004341
Type: Deletion
Location: chr2:27234203 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1199: the 'cpsase b' region; the atp-grasp 2 domain; the 'cpsase (carbamoyl phosphate synthase)' 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.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CAD p.Arg1722Trp Likely pathogenic ★ ⚠ same condition
CAD p.Thr793fs Likely pathogenic ★ same condition
CAD p.Arg1475Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CAD p.Arg1789Gln 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.Gly725fs Pathogenic/Likely pathogenic ★★ 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/cad-p-phe1199fs (accessed [today's date]).

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