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V412=

SynonymousSilentLikely benignTransmembrane · predicted
Synonymous variant · codon at position 412 · Transmembrane helix 4 · WFS1 (Wolframin)

Silent — Silent — but near an exon boundary (splice effect possible)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 412 (Transmembrane helix 4) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — but near an exon boundary (splice effect possible)
Domain
Transmembrane helix 4
Status
—

Therapeutic Implication · Silent

No amino-acid change (V412 is unchanged), so there is no protein-level structural or stability effect. However, this codon sits within 3 residues of the exon junction near protein position 412 — close enough that the nucleotide change could perturb splicing. Worth a SpliceAI check (Wave 2); otherwise expected to be benign at the protein level.

Clinical Evidence

ClinVar classificationBenign/Likely benign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsWolfram syndrome 1
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.1236C>T
Protein consequenceV412=
ClinVar variantNM_006005.3(WFS1):c.1236C>T (p.Val412=)
ClinVar accessionVCV000666780
Last evaluated2022/11/04 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

V412= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 412 (Valine, V) — amino acid unchanged Domain context: Transmembrane helix 4

Schema category: Silent — Silent — but near an exon boundary (splice effect possible)

No amino-acid change (V412 is unchanged), so there is no protein-level structural or stability effect. However, this codon sits within 3 residues of the exon junction near protein position 412 — close enough that the nucleotide change could perturb splicing. Worth a SpliceAI check (Wave 2); otherwise expected to be benign at the protein level.

Clinical evidence

  • Classification: Benign/Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Wolfram syndrome 1
  • cDNA change: c.1236C>T
  • ClinVar accession: VCV000666780
  • Last evaluated: 2022/11/04 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:53:08.904592Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.