CACNA2D2 p.Pro49=
c.147G>A · rs2107205343 · VCV1148157
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00355%, eas)
Conditions
1
early-infantile DEE
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 -0.078 | GERP -0.045, phastCons 0.049 |
| Overall | ||
| CADD | 9.609 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00355%
East Asian · 1/28,138 alleles
Overall
8.53e-05%
1/1,172,718 alleles · very rare
exomes 1/1,021,384 · genomes 0/151,334 · joint denominator
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
- CACNA2D2
- Protein
- p.Pro49=
- Coding
- c.147G>A
- MANE Select
- NM_006030
- dbSNP
- rs2107205343
- Type
- single nucleotide variant
- Location
- chr3:50503277 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.48
Similar variants
- CACNA2D2 p.Pro49Arg Uncertain significance ★ ⚠ same residue
- CACNA2D2 p.Pro49Leu Uncertain significance ★ ⚠ same residue
- CACNA2D2 p.Pro49Ser Likely benign ★ same residue
- CACNA2D2 c.2234+1G>A Likely pathogenic ★★ same condition
- CACNA2D2 p.Gln519Ter Pathogenic/Likely pathogenic ★★ same condition
- CACNA2D2 c.1907+3A>C Uncertain significance ★★ same condition
- CACNA2D2 c.785-3C>T Uncertain significance ★★ same condition
- CACNA2D2 p.Ala1096Thr Uncertain significance ★★ ⚠ 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/cacna2d2-p-pro49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown