CAD p.Val1599=
c.4797C>T · rs747848574 · VCV2980979
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0209%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.11 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.075 | GERP 0.85, phastCons 0.56 |
| Overall | ||
| CADD | 3.866 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0209%
South Asian · 19/91,082 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.00155%
25/1,614,084 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0209% | 4,794 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| European (non-Finnish) | 0.000169% | 590,019 |
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.Val1599=
- Coding
- c.4797C>T
- MANE Select
- NM_004341
- dbSNP
- rs747848574
- Type
- single nucleotide variant
- Location
- chr2:27238124 (GRCh38)
- Gene constraint
- LOEUF 0.409 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.25 · 57 PDB
- Residue 1599
- the 'dhoase (dihydroorotase)' region; an α-helix
Similar variants
- 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
- CAD c.2156+5G>A 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-val1599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown