CACNA2D4 p.Pro1102=
c.3306A>G · rs749266762 · VCV2967323
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -0.66 | GERP -2.5, phastCons 0.049 |
| Overall | ||
| CADD | 3.892 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/90,986 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000248%
4/1,613,092 alleles · very rare
exomes 3/1,460,952 · genomes 1/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,493 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,454 |
| European (non-Finnish) | 8.48e-05% | 1,179,832 |
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
- CACNA2D4
- Protein
- p.Pro1102=
- Coding
- c.3306A>G
- MANE Select
- NM_172364
- dbSNP
- rs749266762
- Type
- single nucleotide variant
- Location
- chr12:1795302 (GRCh38)
- Gene constraint
- LOEUF 1.175 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.69
Similar variants
- CACNA2D4 p.Pro1102Arg Uncertain significance ★ ⚠ same residue
- CACNA2D4 c.1272+1G>C Uncertain significance ★★ same type
- CACNA2D4 c.1644+5G>A Uncertain significance ★★ same type
- CACNA2D4 c.1719+4G>A Uncertain significance ★★ same type
- CACNA2D4 c.1940+5G>A Uncertain significance ★★ same type
- CACNA2D4 c.2055-1G>A Uncertain significance ★★ same type
- CACNA2D4 c.2055-3C>T Uncertain significance ★★ same type
- CACNA2D4 c.2342+5G>T Uncertain significance ★★ same type
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/cacna2d4-p-pro1102 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown