F414=
SynonymousSilentLikely benignTransmembrane · predictedSilent — Silent — but near an exon boundary (splice effect possible)
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 414 (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 Benign/Likely benign for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.
- Wolfram syndrome (classic)autosomal recessive · OMIM 222300submitted as: Wolfram syndrome 1
- 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: 2★ multiple submitters, no conflicts. 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
F414= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 414 (Phenylalanine, F) — amino acid unchanged Domain context: Transmembrane helix 4
Schema category: Silent — Silent — but near an exon boundary (splice effect possible)
No amino-acid change (F414 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
Benign/Likely benign — for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)
ClinVar classifies this variant as Benign/Likely benign for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.
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: Benign/Likely benign
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: Wolfram syndrome 1
- cDNA change: c.1242C>T
- ClinVar accession: VCV000513249
- Last evaluated: 2025/12/15 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:53:10.532857Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.