Is CAD p.Pro204Ser (c.610C>T) pathogenic?

CAD p.Pro204Ser (c.610C>T) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely pathogenic (0.6656); Ultra-rare (popmax 0.0165%, mid); Associated with developmental and epileptic encephalopathy, 50.

What condition is associated with CAD p.Pro204Ser (c.610C>T)?

CAD p.Pro204Ser (c.610C>T) is associated with developmental and epileptic encephalopathy, 50 (ClinVar).

How common is CAD p.Pro204Ser (c.610C>T) in the general population?

CAD p.Pro204Ser (c.610C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is CAD-CDG inherited?

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

What do computational predictors say about CAD p.Pro204Ser (c.610C>T)?

AlphaMissense predicts likely pathogenic (score 0.6656) — an in-silico prediction, not a clinical call.

CAD p.Pro204Ser

c.610C>T · rs1675229364 · VCV2921063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6656 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 50

Computational evidence

Protein change
AlphaMissense	0.6656	likely pathogenic
REVEL	0.921	moderately pathogenic-leaning
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 5,475 bp · p 0.17 · regional, not allelic
Overall
CADD	26.6	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 0.0165% Middle Eastern · 1/6,060 alleles

Overall 6.2e-05% 1/1,613,998 alleles · ultra-rare exomes 1/1,461,762 · genomes 0/152,236 · joint denominator

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.Pro204Ser
Coding: c.610C>T
MANE Select: NM_004341
dbSNP: rs1675229364
Type: single nucleotide variant
Location: chr2:27222633 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 204: 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.Pro204= 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.Met33Arg Pathogenic ★★ same condition
CAD c.4315-3C>T Uncertain significance ★★ same condition
CAD c.996-13A>G 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-pro204ser (accessed [today's date]).

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