Is CAD p.Phe312fs (c.933_934del) pathogenic?

CAD p.Phe312fs (c.933934del) is classified Pathogenic in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). Absent from gnomAD; Associated with developmental and epileptic encephalopathy, 50.

What condition is associated with CAD p.Phe312fs (c.933_934del)?

CAD p.Phe312fs (c.933_934del) is associated with developmental and epileptic encephalopathy, 50 (ClinVar).

How common is CAD p.Phe312fs (c.933_934del) in the general population?

CAD p.Phe312fs (c.933_934del) is absent from gnomAD (gnomAD).

How is CAD-CDG inherited?

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

CAD p.Phe312fs

c.933_934del · rs2465293335 · VCV3254721

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

developmental and epileptic encephalopathy, 50

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 7 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.1	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAD
Protein: p.Phe312fs
Coding: c.933_934del
MANE Select: NM_004341
dbSNP: rs2465293335
Type: Microsatellite
Location: chr2:27223682 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 312: the glutamine amidotransferase type-1 domain; the 'gatase (glutamine amidotransferase)' region

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

Disease context

developmental and epileptic encephalopathy, 50 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CAD-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CAD p.Phe312= Likely benign ★ same residue
CAD p.Arg1789Ter Pathogenic ★★ same condition
CAD p.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CAD p.Arg191Ter Pathogenic ★★ same condition
CAD p.Gln1604Ter Likely pathogenic ★★ same condition
CAD p.Gln1913fs Pathogenic/Likely pathogenic ★★ same condition
CAD p.Met33Arg Pathogenic ★★ same condition
CAD c.4315-3C>T Uncertain significance ★★ 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-phe312fs (accessed [today's date]).

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