CC2D2A p.Cys1112=
c.3336C>T · rs2475074578 · VCV2111658
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
2
Joubert syndrome
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 -1, phastCons 1 |
| Overall | ||
| CADD | 9.696 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,416 alleles
Overall
0.000138%
2/1,453,092 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,416 |
| European (non-Finnish) | 8.49e-05% | 1,177,862 |
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
- CC2D2A
- Protein
- p.Cys1112=
- Coding
- c.3336C>T
- MANE Select
- NM_001378615
- dbSNP
- rs2475074578
- Type
- single nucleotide variant
- Location
- chr4:15567724 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 69.46
- Residue 1112
- the c2 domain
Similar variants
- CC2D2A p.Cys1112Ter Pathogenic ★ same residue
- CC2D2A p.Cys1112Gly Uncertain significance ★ ⚠ same residue
- CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CC2D2A c.123+2T>G Likely pathogenic ★★ same condition
- CC2D2A c.1359+1G>C Likely pathogenic ★★ same condition
- CC2D2A c.1466+1G>A Likely pathogenic ★★ same condition
- CC2D2A c.1466+2T>C Likely pathogenic ★★ same condition
- CC2D2A c.1608-2A>G 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/cc2d2a-p-cys1112 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown