CDC45 p.Pro128=
c.384C>T · rs747335297 · VCV3017941
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0658%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.1 | GERP -3.1 |
| Overall | ||
| CADD | 2.087 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0658%
Middle Eastern · 4/6,082 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.00124%
20/1,613,282 alleles · ultra-rare
exomes 17/1,461,134 · genomes 3/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0658% | 1,521 |
| Admixed American | 0.00501% | 19,943 |
| African / African-American | 0.00267% | 37,434 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
| South Asian | 0.0011% | 90,860 |
| European (non-Finnish) | 0.000763% | 131,087 |
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.Pro128=
- Coding
- c.384C>T
- MANE Select
- NM_003504
- dbSNP
- rs747335297
- Type
- single nucleotide variant
- Location
- chr22:19483903 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.59 · 7 PDB
- Residue 128
- an α-helix
Similar variants
- CDC45 p.Pro128Ala Uncertain significance ★ ⚠ same residue
- 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
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-pro128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown