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A874=

SynonymousSilentLikely benignLumenal · predicted
Synonymous variant · codon at position 874 · C-terminal ER-lumenal (calcium binding, calmodulin, chaperone) · 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 874 (C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
Status
—

Therapeutic Implication · Silent

No amino-acid change (A874 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 classificationBenign/Likely benign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsWolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; Wolfram-like syndrome
Population frequency (gnomAD v4)Low frequency · AF 0.014%
cDNA changec.2622C>T
Protein consequenceA874=
ClinVar variantNM_006005.3(WFS1):c.2622C>T (p.Ala874=)
ClinVar accessionVCV000378861
Last evaluated2026/01/15 00:00

Observed in the general population.

Therapeutic Strategy Handoff · prediction

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Full Variant Card

A874= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 874 (Alanine, A) — amino acid unchanged Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)

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

No amino-acid change (A874 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: Benign/Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; Wolfram-like syndrome
  • cDNA change: c.2622C>T
  • ClinVar accession: VCV000378861
  • Last evaluated: 2026/01/15 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:56:57.060705Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.