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L381=

SynonymousSilentLikely benignTransmembrane · predicted
Synonymous variant · codon at position 381 · Transmembrane helix 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 381 (Transmembrane helix 3) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
Transmembrane helix 3
Status
—

Therapeutic Implication · Silent

No amino-acid change (L381 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 conditionsType 2 diabetes mellitus; Wolfram syndrome 1; Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.1143G>A
Protein consequenceL381=
ClinVar variantNM_006005.3(WFS1):c.1143G>A (p.Leu381=)
ClinVar accessionVCV000289307
Last evaluated2026/01/27 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

L381= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 381 (Leucine, L) — amino acid unchanged Domain context: Transmembrane helix 3

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

No amino-acid change (L381 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: Type 2 diabetes mellitus; Wolfram syndrome 1; Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6
  • cDNA change: c.1143G>A
  • ClinVar accession: VCV000289307
  • Last evaluated: 2026/01/27 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:52:46.012261Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.