CDC45 p.Ala560=
c.1680A>G · rs746649567 · VCV2121658
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -7 | GERP -2.9 |
| Overall | ||
| CADD | 0.065 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,080 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00062%
10/1,613,904 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,180 |
| East Asian | 0.00223% | 44,884 |
| Admixed American | 0.00167% | 59,986 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 8.47e-05% | 1,179,965 |
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.Ala560=
- Coding
- c.1680A>G
- MANE Select
- NM_003504
- dbSNP
- rs746649567
- Type
- single nucleotide variant
- Location
- chr22:19518887 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.59 · 7 PDB
- Residue 560
- a UniProt-annotated variant site (in mgors7; likely pathogenic); 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-ala560 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown