Is CAD p.Ser332= (c.996T>C) pathogenic?

CAD p.Ser332= (c.996T>C) is classified Likely benign in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with CAD p.Ser332= (c.996T>C)?

CAD p.Ser332= (c.996T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CAD p.Ser332= (c.996T>C) in the general population?

CAD p.Ser332= (c.996T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CAD p.Ser332=

c.996T>C · VCV3826808

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Inborn genetic diseases

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 0.67	GERP -2.2, phastCons 1
Overall
CADD	12.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,064 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000975%

Overall 0.00149% 24/1,607,742 alleles · ultra-rare exomes 18/1,455,636 · genomes 6/152,106 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,064
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,552
European (non-Finnish)	0.00179%	55,921
African / African-American	0.00134%	74,764

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.Ser332=
Coding: c.996T>C
MANE Select: NM_004341
Type: single nucleotide variant
Location: chr2:27223917 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 332: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAD c.6480+6T>C Uncertain significance ★★ same condition
CAD p.Ala1527Thr Uncertain significance ★★ ⚠ same condition
CAD p.Ala1769Thr Uncertain significance ★★ ⚠ same condition
CAD p.Ala1824Ser Uncertain significance ★★ ⚠ same condition
CAD p.Ala495Pro Uncertain significance ★★ ⚠ same condition
CAD p.Ala608Thr Uncertain significance ★★ ⚠ same condition
CAD p.Arg1075His Uncertain significance ★★ ⚠ same condition
CAD p.Arg1181Gln 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-ser332 (accessed [today's date]).

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