RareResearch.AI
← Back to atlas

T436=

SynonymousSilentBenignTransmembrane · predicted
Synonymous variant · codon at position 436 · Transmembrane helix 5 · WFS1 (Wolframin)

Silent — Silent — no amino-acid change

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
Fullscreen ↗

AlphaFold wild-type wolframin · the variant site near residue 436 (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 (T436 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
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsWFS1-Related Spectrum Disorders; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.1308C>T
Protein consequenceT436=
ClinVar variantNM_006005.3(WFS1):c.1308C>T (p.Thr436=)
ClinVar accessionVCV000045433
Last evaluated2026/03/01 00:00

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

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the T436= card below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals matched to this Silent synonymous variant and its domain context.

Download T436= PDF card ↓or markdown ↓

Full Variant Card

T436= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 436 (Threonine, T) — amino acid unchanged Domain context: Transmembrane helix 5

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

No amino-acid change (T436 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
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: WFS1-Related Spectrum Disorders; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6
  • cDNA change: c.1308C>T
  • ClinVar accession: VCV000045433
  • Last evaluated: 2026/03/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:53:17.850840Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.