CDC45 p.Ala298=
c.894C>T · rs141196987 · VCV1594311
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0256%, nfe)
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 2.7 | GERP 0.87, phastCons 1 |
| Overall | ||
| CADD | 12.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0256%
European (non-Finnish) · 302/1,180,020 alleles
Filtering AF
0.0231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0223%
Overall
0.0195%
314/1,614,176 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0256% | 3,907 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| Admixed American | 0.005% | 20,008 |
| African / African-American | 0.004% | 25,021 |
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.Ala298=
- Coding
- c.894C>T
- MANE Select
- NM_003504
- dbSNP
- rs141196987
- Type
- single nucleotide variant
- Location
- chr22:19507455 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.59 · 7 PDB
- Residue 298
- a UniProt-annotated variant site (in mgors7; decreased protein level); an α-helix
Similar variants
- CDC45 p.Ala298Val Likely pathogenic ★ ⚠ same residue
- CDC45 p.Ala298Asp 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
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-ala298 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown