L410=
SynonymousSilentLikely benignTransmembrane · predictedSilent — Silent — but near an exon boundary (splice effect possible)
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 410 (Transmembrane helix 4) is highlighted.
Variant Assessment
Therapeutic Implication · Silent
Clinical Evidence
Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).
ClinVar classifies this variant as Likely benign, 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: 1★ single submitter. 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.
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Full Variant Card
L410= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 410 (Leucine, L) — amino acid unchanged Domain context: Transmembrane helix 4
Schema category: Silent — Silent — but near an exon boundary (splice effect possible)
No amino-acid change (L410 is unchanged), so there is no protein-level structural or stability effect. However, this codon sits within 3 residues of the exon junction near protein position 412 — close enough that the nucleotide change could perturb splicing. Worth a SpliceAI check (Wave 2); otherwise expected to be benign at the protein level.
Clinical evidence
Inheritance and scope
Likely benign — phenotype scope not stated in ClinVar
ClinVar classifies this variant as Likely benign, 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.
- Classification: Likely benign
- Review status: criteria provided, single submitter
- cDNA change: c.1230C>G
- ClinVar accession: VCV002178886
- Last evaluated: 2024/04/30 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:53:05.438766Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.