CAD p.Phe2129=
c.6387C>T · rs141620726 · VCV2416366
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.22 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.7 | GERP -4.3 |
| Overall | ||
| CADD | 4.883 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,932 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000744%
12/1,613,948 alleles · very rare
exomes 10/1,461,740 · genomes 2/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,466 |
| South Asian | 0.0022% | 45,536 |
| European (non-Finnish) | 0.000678% | 147,492 |
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.Phe2129=
- Coding
- c.6387C>T
- MANE Select
- NM_004341
- dbSNP
- rs141620726
- Type
- single nucleotide variant
- Location
- chr2:27242880 (GRCh38)
- Gene constraint
- LOEUF 0.409 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.25 · 57 PDB
- Residue 2129
- a UniProt-annotated variant site (in dee50; uncertain significance); the 'atcase (aspartate transcarbamylase)' region; a β-strand
Similar variants
- CAD p.Phe2129fs Pathogenic ★ 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-phe2129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown