CDC45 p.Leu30=
c.88C>T · rs4141527 · VCV1168874
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11%, eas) — too common for a highly-penetrant pathogenic allele
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 0.77 | GERP -0.2, phastCons 0.28 |
| Overall | ||
| CADD | 13.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11%
East Asian · 4,926/44,854 alleles
Filtering AF
10.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.6%
Overall
3.16%
50,945/1,613,868 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 11% | 9 |
| Admixed American | 9.96% | 10 |
| African / African-American | 8.61% | 12 |
| South Asian | 8.57% | 12 |
| Finnishnot grpmax-eligible | 4.43% | 23 |
| Remaining individualsnot grpmax-eligible | 3.58% | 28 |
| European (non-Finnish) | 1.71% | 59 |
| Ashkenazi Jewishnot grpmax-eligible | 1.69% | 59 |
| Middle Eastern | 1.4% | 71 |
| Amishnot grpmax-eligible | 0.22% | 455 |
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.Leu30=
- Coding
- c.88C>T
- MANE Select
- NM_003504
- dbSNP
- rs4141527
- Type
- single nucleotide variant
- Location
- chr22:19480194 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.59 · 7 PDB
- Residue 30
- an α-helix
Similar variants
- 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
- CDC45 p.Arg251His Uncertain significance ★★ ⚠ same type
- CDC45 p.Arg269Trp 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-leu30 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown