CCDC8 p.Pro245=
c.735G>C · VCV4853130
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -2.6 | GERP -3 |
| Overall | ||
| CADD | 0.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,878 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00113%
18/1,599,752 alleles · very rare
exomes 17/1,447,540 · genomes 1/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,878 |
| European (non-Finnish) | 0.00136% | 73,747 |
| African / African-American | 0.00133% | 74,934 |
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
- CCDC8
- Protein
- p.Pro245=
- Coding
- c.735G>C
- MANE Select
- NM_032040
- Type
- single nucleotide variant
- Location
- chr19:46412076 (GRCh38)
- Gene constraint
- LOEUF 1.796 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 46.83 · 1 PDB
- Residue 245
- the 'disordered' region
Similar variants
- CCDC8 p.Ala217Thr Uncertain significance ★★ ⚠ same type
- CCDC8 p.Ala293Thr Uncertain significance ★★ ⚠ same type
- CCDC8 p.Ala393Val Uncertain significance ★★ ⚠ same type
- CCDC8 p.Ala527Val Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg15Gln Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg225Gly Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg277His Uncertain significance ★★ ⚠ same type
- CCDC8 p.Arg277Ser 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/ccdc8-p-pro245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown