CAD p.Ala1272=
c.3816G>A · rs749232399 · VCV1435431
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.99 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.67 | gain · loss 0.24 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -1.2, phastCons 1 |
| Overall | ||
| CADD | 24.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,810 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.00161%
26/1,611,434 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,405 |
| European (non-Finnish) | 0.00178% | 56,141 |
| Admixed American | 0.00168% | 59,590 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,356 |
| African / African-American | 0.00134% | 74,804 |
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.Ala1272=
- Coding
- c.3816G>A
- MANE Select
- NM_004341
- dbSNP
- rs749232399
- Type
- single nucleotide variant
- Location
- chr2:27235274 (GRCh38)
- Gene constraint
- LOEUF 0.409 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.25 · 57 PDB
- Residue 1272
- the 'cpsase b' region; the 'cpsase (carbamoyl phosphate synthase)' region
Similar variants
- CAD p.Ala1272Val Uncertain significance ★ ⚠ same residue
- CAD p.Arg1789Ter Pathogenic ★★ same type
- CAD p.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- CAD p.Arg191Ter Pathogenic ★★ same type
- CAD p.Gln1604Ter Likely pathogenic ★★ same type
- CAD p.Met33Arg Pathogenic ★★ same type
- CAD c.1254+6G>A Uncertain significance ★★ same type
- CAD c.2032-3C>T Uncertain significance ★★ 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-ala1272 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown