c.832+1G>A
SpliceS3Pathogenic/Likely pathogenicCytoplasmic · predictedS3 — SpliceAI could not score this variant — wet-lab validation
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 278 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted. The SpliceAI isoform prediction that resolves the exact structural outcome is computing and backfills here.
Variant Assessment
Computational depth pending. The schema call above is from sequence-level analysis. The SpliceAI isoform prediction that resolves the definitive structural/splicing outcome is computing and backfills onto this card (Wave 2).
Therapeutic Implication · S3
Clinical Evidence
Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).
ClinVar classifies this variant as Pathogenic/Likely pathogenic, but does not state what it is classified for. ClinVar records no condition for this variant. A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.
- Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient.
- Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
Review status: no ClinVar review status recorded. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.
No population breakdown — the variant is absent from gnomAD v4, so no ancestry group has an observed frequency.
No homozygotes — the variant is absent from gnomAD v4 altogether.
Source: gnomAD r4, retrieved 2026-08-21. Values are allele frequencies. The carrier estimate is derived from the allele frequency (Hardy-Weinberg, ~2·AF) and is an approximation, not a published figure — where a published carrier frequency exists it outranks this column and is cited on the card.
Feed this card to Wolfram Intelligence
Download the c.832+1G>A card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this S3 splice variant and its domain context.
Full Variant Card
c.832+1G_A — WFS1 Molecular Atlas Card
Variant type: Splice site Boundary: donor (5' splice site) · intronic offset +1 Nearest protein position: ~278 (N-terminal cytoplasmic (intrinsically disordered))
Schema category: S3 — SpliceAI could not score this variant — wet-lab validation
SpliceAI returned no usable prediction (no genomic coordinate / SpliceAI record). The canonical splice-region call stands; wet-lab RNA validation is required to resolve the isoform.
Splice prediction
- Affected site: donor (5' splice site), canonical (±1/±2 core)
- SpliceAI: no genomic coordinate / SpliceAI record
Clinical evidence
Inheritance and scope
Pathogenic/Likely pathogenic — phenotype scope not stated in ClinVar
ClinVar classifies this variant as Pathogenic/Likely pathogenic, but does not state what it is classified for. ClinVar records no condition for this variant. A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.
Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient. Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
Not found in the cached WFS1 ClinVar set (_reference/WFS1_clinvar_variants.csv).
Card generated by wolfram-atlas-batch (splice pipeline) on 2026-06-08T07:53:13.337833Z.
Schema: reference/card_schema_extension.md (S1–S3). WFS1: UniProt O76024, AlphaFold v6.