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P453=

SynonymousSilentConflictingTransmembrane · predicted
Synonymous variant · codon at position 453 · Cytoplasmic loop 3 · WFS1 (Wolframin)

Silent — Silent — no amino-acid change

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 453 (Cytoplasmic loop 3) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
Cytoplasmic loop 3
Status
—

Therapeutic Implication · Silent

No amino-acid change (P453 is unchanged): the codon is altered but the protein sequence is identical to wild-type. No structural, stability or AlphaMissense effect applies. Synonymous variants are typically benign unless they affect splicing or regulatory elements; this one is not adjacent to an exon boundary.

Clinical Evidence

ClinVar classificationConflicting classifications of pathogenicity
Review statuscriteria provided, conflicting classifications
Associated conditionsWolfram syndrome 1; Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
Population frequency (gnomAD v4)Ultra-rare · AF 0.0023%
cDNA changec.1359C>T
Protein consequenceP453=
ClinVar variantNM_006005.3(WFS1):c.1359C>T (p.Pro453=)
ClinVar accessionVCV002163228
Last evaluated2025/03/16 00:00

Observed at very low frequency in gnomAD.

Therapeutic Strategy Handoff · prediction

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Full Variant Card

P453= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 453 (Proline, P) — amino acid unchanged Domain context: Cytoplasmic loop 3

Schema category: Silent — Silent — no amino-acid change

No amino-acid change (P453 is unchanged): the codon is altered but the protein sequence is identical to wild-type. No structural, stability or AlphaMissense effect applies. Synonymous variants are typically benign unless they affect splicing or regulatory elements; this one is not adjacent to an exon boundary.

Clinical evidence

  • Classification: Conflicting classifications of pathogenicity
  • Review status: criteria provided, conflicting classifications
  • Associated conditions: Wolfram syndrome 1; Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
  • cDNA change: c.1359C>T
  • ClinVar accession: VCV002163228
  • Last evaluated: 2025/03/16 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:53:26.724658Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.