CDC45 p.Glu273=
c.819G>A · VCV3712270
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0242%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.69 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 7.182 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0242%
South Asian · 22/91,086 alleles
Filtering AF
0.0163%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.00155%
25/1,613,996 alleles · ultra-rare
exomes 23/1,461,758 · genomes 2/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0242% | 4,140 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
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.Glu273=
- Coding
- c.819G>A
- MANE Select
- NM_003504
- Type
- single nucleotide variant
- Location
- chr22:19505476 (GRCh38)
- Gene constraint
- LOEUF 0.77 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.59 · 7 PDB
- Residue 273
- a β-strand
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-glu273 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown