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G437=

SynonymousSilentConflictingTransmembrane · predicted
Synonymous variant · codon at position 437 · Transmembrane helix 5 · 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 437 (Transmembrane helix 5) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
Transmembrane helix 5
Status
—

Therapeutic Implication · Silent

No amino-acid change (G437 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 conditionsAutosomal dominant nonsyndromic hearing loss 6; WFS1-Related Spectrum Disorders; Wolfram syndrome 1
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.1311C>T
Protein consequenceG437=
ClinVar variantNM_006005.3(WFS1):c.1311C>T (p.Gly437=)
ClinVar accessionVCV000349317
Last evaluated2018/01/12 00:00

Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).

Therapeutic Strategy Handoff · prediction

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Full Variant Card

G437= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 437 (Glycine, G) — amino acid unchanged Domain context: Transmembrane helix 5

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

No amino-acid change (G437 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: Autosomal dominant nonsyndromic hearing loss 6; WFS1-Related Spectrum Disorders; Wolfram syndrome 1
  • cDNA change: c.1311C>T
  • ClinVar accession: VCV000349317
  • Last evaluated: 2018/01/12 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:53:18.770592Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.