Is CAD p.Ala544= (c.1632C>T) pathogenic?

CAD p.Ala544= (c.1632C>T) is classified Benign/Likely benign in CAD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.274%, sas); Associated with developmental and epileptic encephalopathy, 50.

What condition is associated with CAD p.Ala544= (c.1632C>T)?

CAD p.Ala544= (c.1632C>T) is associated with developmental and epileptic encephalopathy, 50 (ClinVar).

How common is CAD p.Ala544= (c.1632C>T) in the general population?

CAD p.Ala544= (c.1632C>T) is rare (popmax 0.274%, sas) (gnomAD).

How is CAD-CDG inherited?

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

CAD p.Ala544=

c.1632C>T · rs146242038 · VCV732083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.274%, sas)

Conditions

developmental and epileptic encephalopathy, 50

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -5
Overall
CADD	1.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.274% South Asian · 250/91,078 alleles

Filtering AF 0.247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.169% 2,720/1,613,708 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.274%	364
European (non-Finnish)	0.191%	522
Remaining individualsnot grpmax-eligible	0.11%	906
Admixed American	0.085%	1,177
Finnishnot grpmax-eligible	0.0766%	1,305
Middle Eastern	0.0661%	1,513
African / African-American	0.04%	2,502
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
East Asian	0.00446%	22,440

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.Ala544=
Coding: c.1632C>T
MANE Select: NM_004341
dbSNP: rs146242038
Type: single nucleotide variant
Location: chr2:27225716 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 544: the atp-grasp 1 domain; the 'cpsase (carbamoyl phosphate synthase)' region; the 'cpsase a' 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.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
CAD c.996-4A>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-ala544 (accessed [today's date]).

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