CACNA1A p.Ser331Ter
c.992C>G · rs1555767930 · VCV523906
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 47 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 0.82, phastCons 1 |
| Overall | ||
| CADD | 43.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CACNA1A
- Protein
- p.Ser331Ter
- Coding
- c.992C>G
- MANE Select
- NM_001127222
- dbSNP
- rs1555767930
- Type
- single nucleotide variant
- Location
- chr19:13335896 (GRCh38)
- Gene constraint
- LOEUF 0.331 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.34 · 4 PDB
- Residue 331
- an α-helix
Similar variants
- CACNA1A c.1082+1G>A Pathogenic ★★ same type
- CACNA1A c.1198+1G>A Pathogenic/Likely pathogenic ★★ same type
- CACNA1A c.2105-2A>G Likely pathogenic ★★ same type
- CACNA1A c.3692+1G>A Pathogenic/Likely pathogenic ★★ same type
- CACNA1A c.3822+1G>A Pathogenic ★★ same type
- CACNA1A c.3989+1G>A Pathogenic ★★ same type
- CACNA1A c.3989+1G>T Pathogenic ★★ same type
- CACNA1A c.3990-2A>G Pathogenic/Likely pathogenic ★★ 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/cacna1a-p-ser331ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown