CAD p.Pro976=
c.2928A>G · rs367879254 · VCV1578731
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0114%, nfe)
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 0.2 | GERP -5, phastCons 0.33 |
| Overall | ||
| CADD | 7.607 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0114%
European (non-Finnish) · 134/1,179,452 alleles
Filtering AF
0.00978%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00919%
Overall
0.00936%
151/1,613,442 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0114% | 8,802 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,924 |
| Admixed American | 0.00833% | 12,001 |
| African / African-American | 0.00667% | 14,984 |
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.Pro976=
- Coding
- c.2928A>G
- MANE Select
- NM_004341
- dbSNP
- rs367879254
- Type
- single nucleotide variant
- Location
- chr2:27233077 (GRCh38)
- Gene constraint
- LOEUF 0.409 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.25 · 57 PDB
- Residue 976
- the 'cpsase b' region; the 'cpsase (carbamoyl phosphate synthase)' region
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-pro976 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown