CC2D2A p.Leu353=
c.1057C>T · rs1365896129 · VCV1654930
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
2
Joubert syndrome
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 1.3 | GERP -1.4, phastCons 0.72 |
| Overall | ||
| CADD | 7.44 | 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
Overall
0.00031%
5/1,613,162 alleles · very rare
exomes 4/1,460,972 · genomes 1/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,878 |
| Admixed American | 0.00167% | 59,944 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,444 |
| African / African-American | 0.00133% | 74,920 |
| European (non-Finnish) | 8.48e-05% | 1,179,490 |
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.Leu353=
- Coding
- c.1057C>T
- MANE Select
- NM_001378615
- dbSNP
- rs1365896129
- Type
- single nucleotide variant
- Location
- chr4:15516664 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 69.46
Similar variants
- 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
- CC2D2A c.2004-17A>G Pathogenic/Likely pathogenic ★★ same condition
- CC2D2A c.2486+1G>A 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-leu353 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown