Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 48.6%, mid) — too common for a highly-penetrant pathogenic allele
Conditions
1
primary ciliary dyskinesia 15
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 -0.65 | GERP -2 |
| Non-coding constraint | Z 2.10 | 1 kb window · o/e 0.84 · regional · uncalibrated |
| Overall | ||
| CADD | 0.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
48.6%
Middle Eastern · 1,150/2,364 alleles
Filtering AF
47.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 47%
Overall
35.2%
231,634/658,676 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 48.6% | 2 |
| African / African-American | 47.7% | 2 |
| Finnishnot grpmax-eligible | 41.8% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 41.6% | 2 |
| South Asian | 40.6% | 2 |
| Remaining individualsnot grpmax-eligible | 36% | 3 |
| European (non-Finnish) | 34.3% | 3 |
| Amishnot grpmax-eligible | 24.8% | 4 |
| Admixed American | 23.3% | 4 |
| East Asian | 17.4% | 6 |
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
- CCDC40
- Coding
- c.*186A>C
- MANE Select
- NM_017950
- dbSNP
- rs2304851
- Type
- single nucleotide variant
- Location
- chr17:80099961 (GRCh38)
- Gene constraint
- LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.70 · 1 PDB
Disease context
primary ciliary dyskinesia 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Primary ciliary dyskinesia (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, X-linked recessive
- Onset
- Neonatal
- Prevalence
- 1-5 / 10 000 (Pakistan)
Similar variants
- CCDC40 c.1159+1G>A Likely pathogenic ★★ same condition
- CCDC40 c.2712-1G>T Pathogenic/Likely pathogenic ★★ same condition
- CCDC40 c.940-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CCDC40 p.Arg1059Ter Pathogenic/Likely pathogenic ★★ same condition
- CCDC40 p.Arg301Ter Pathogenic/Likely pathogenic ★★ same condition
- CCDC40 p.Arg321Ter Pathogenic ★★ same condition
- CCDC40 p.Arg449Ter Pathogenic ★★ same condition
- CCDC40 p.Gln142Ter Pathogenic/Likely pathogenic ★★ 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/ccdc40-c-star-186a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown