CAD p.Pro386=
c.1158C>T · rs541054613 · VCV726316
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0466%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -4.1 |
| Overall | ||
| CADD | 0.901 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0466%
Admixed American · 28/60,024 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0286%
Overall
0.0198%
319/1,614,192 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0466% | 2,144 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| European (non-Finnish) | 0.0228% | 4,387 |
| African / African-American | 0.00666% | 15,012 |
| East Asian | 0.00223% | 44,884 |
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.Pro386=
- Coding
- c.1158C>T
- MANE Select
- NM_004341
- dbSNP
- rs541054613
- Type
- single nucleotide variant
- Location
- chr2:27224394 (GRCh38)
- Gene constraint
- LOEUF 0.409 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.25 · 57 PDB
- Residue 386
- the 'linker' region
Similar variants
- CAD p.Pro386Ser 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-pro386 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown