Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.6%, sas)
Conditions
1
Meier-Gorlin syndrome 5
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 -1.7 | GERP 0.72 |
| Overall | ||
| CADD | 5.432 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.6%
South Asian · 2,365/91,084 alleles
Filtering AF
2.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.47%
Overall
0.157%
2,533/1,613,860 alleles · low-frequency
exomes 2,366/1,461,512 · genomes 167/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.6% | 39 |
| Remaining individualsnot grpmax-eligible | 0.182% | 548 |
| Middle Eastern | 0.0825% | 1,212 |
| Admixed American | 0.005% | 20,007 |
| African / African-American | 0.004% | 25,020 |
| European (non-Finnish) | 0.00356% | 28,088 |
| East Asian | 0.00223% | 44,882 |
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.Ser504=
- Coding
- c.1512A>G
- MANE Select
- NM_001254
- dbSNP
- rs4135031
- Type
- single nucleotide variant
- Location
- chr17:40301527 (GRCh38)
- Gene constraint
- LOEUF 0.99 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 69.85 · 7 PDB
Similar variants
- CDC6 p.Ser504Leu Uncertain significance ★ ⚠ same residue
- CDC6 p.Arg378His Uncertain significance ★★ same condition
- CDC6 p.Lys531Glu Uncertain significance ★★ ⚠ same condition
- CDC6 p.Val282Ala Uncertain significance ★★ ⚠ same condition
- CDC6 c.*653C>A Likely benign ★★ same condition
- CDC6 p.Asp295Asn Benign ★★ same condition
- CDC6 p.Cys146= Benign ★★ same condition
- CDC6 p.Pro55= Benign/Likely benign ★★ same condition
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-ser504 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown