CDC6 p.Leu355=
c.1065G>A · VCV4935067
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
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 0.054 | GERP -1.7, phastCons 0.46 |
| Overall | ||
| CADD | 2.647 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,870 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.000434%
7/1,614,016 alleles · ultra-rare
exomes 6/1,461,744 · genomes 1/152,272 · joint denominator
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
- CDC6
- Protein
- p.Leu355=
- Coding
- c.1065G>A
- MANE Select
- NM_001254
- Type
- single nucleotide variant
- Location
- chr17:40294485 (GRCh38)
- Gene constraint
- LOEUF 0.99 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.85 · 7 PDB
Similar variants
- CDC6 p.Arg21Gln Uncertain significance ★★ ⚠ same type
- CDC6 p.Arg21Trp Uncertain significance ★★ ⚠ same type
- CDC6 p.Arg325Ser Uncertain significance ★★ ⚠ same type
- CDC6 p.Arg378Cys Uncertain significance ★★ same type
- CDC6 p.Arg378His Uncertain significance ★★ same type
- CDC6 p.Arg494Cys Uncertain significance ★★ ⚠ same type
- CDC6 p.Arg528His Uncertain significance ★★ ⚠ same type
- CDC6 p.Asn118Lys 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/cdc6-p-leu355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown