CDC45 p.Leu473=
c.1417C>T · rs1015221471 · VCV3050041
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
CDC45-related disorder
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 |
|---|---|---|
| Pangolin | Δ0.25 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 9.221 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,944 alleles
Overall
0.000124%
2/1,611,800 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,944 |
| South Asian | 0.0011% | 90,872 |
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
- CDC45
- Protein
- p.Leu473=
- Coding
- c.1417C>T
- MANE Select
- NM_003504
- dbSNP
- rs1015221471
- Type
- single nucleotide variant
- Location
- chr22:19515025 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.59 · 7 PDB
- Residue 473
- a UniProt-annotated variant site (in mgors7; likely pathogenic); an α-helix
Disease context
CDC45-related disorder
Similar variants
- CDC45 p.Tyr188Ter Likely pathogenic ★ same condition
- CDC45 p.Arg554Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
- CDC45 p.Pro463Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
- CDC45 c.653+4C>T Uncertain significance ★★ same type
- CDC45 p.Ala373Val Uncertain significance ★★ ⚠ same type
- CDC45 p.Ala38Asp Uncertain significance ★★ ⚠ same type
- CDC45 p.Arg157His Uncertain significance ★★ ⚠ same type
- CDC45 p.Arg175Gln 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/cdc45-p-leu473 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown