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E249=

SynonymousSilentLikely benignCytoplasmic · predicted
Synonymous variant · codon at position 249 · N-terminal cytoplasmic (intrinsically disordered) · 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 249 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
N-terminal cytoplasmic (intrinsically disordered)
Status
—

Therapeutic Implication · Silent

No amino-acid change (E249 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 classificationLikely benign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsAutosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Cataract 41; Wolfram syndrome 1
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.747G>A
Protein consequenceE249=
ClinVar variantNM_006005.3(WFS1):c.747G>A (p.Glu249=)
ClinVar accessionVCV000738569
Last evaluated2023/12/01 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

E249= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 249 (Glutamic acid, E) — amino acid unchanged Domain context: N-terminal cytoplasmic (intrinsically disordered)

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

No amino-acid change (E249 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: Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Cataract 41; Wolfram syndrome 1
  • cDNA change: c.747G>A
  • ClinVar accession: VCV000738569
  • Last evaluated: 2023/12/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:51:46.229123Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.