CACNA2D2 p.Val558=
c.1674G>A · rs201381985 · VCV771083
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.105%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -0.18, phastCons 1 |
| Overall | ||
| CADD | 11.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.105%
East Asian · 47/44,882 alleles
Filtering AF
0.0808%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0725%
Overall
0.00304%
49/1,613,550 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.105% | 955 |
| Admixed American | 0.00167% | 60,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,500 |
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.Val558=
- Coding
- c.1674G>A
- MANE Select
- NM_006030
- dbSNP
- rs201381985
- Type
- single nucleotide variant
- Location
- chr3:50376141 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.48
- Residue 558
- a disulfide bond; the cache domain
Similar variants
- CACNA2D2 p.Val558Leu Uncertain significance ★ ⚠ same residue
- CACNA2D2 p.Val558Met Uncertain significance ★★ ⚠ 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
- CACNA2D2 p.Ala253Thr 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-val558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown