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L548V

AlphaMissense: likely benign (0.21)Uncertain significanceTransmembrane · predicted
LeucineValine at position 548 · Transmembrane helix 8 · WFS1 (Wolframin)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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Computational Predictions

AlphaMissense
0.207
likely benign
AlphaFold pLDDT
86
model confidence
DynaMut2 ΔΔG
pending
not yet computed
ClinVar
Uncertain significance
Uncertain significance

AlphaMissense + AlphaFold card. This variant is mapped from AlphaMissense pathogenicity and AlphaFold confidence. The DynaMut2 ΔΔG stability prediction and the wild-type/mutant structural comparison (dual-pane + bond network) are computed per-variant and backfill here — they require a DynaMut2 submission, unlike the precomputed AlphaMissense score.

Clinical Evidence

ClinVar classificationUncertain significance
Review statuscriteria provided, single submitter
Associated conditionsAutosomal dominant nonsyndromic hearing loss 6; Cataract 41; Wolfram syndrome 1; Wolfram-like syndrome; Type 2 diabetes mellitus
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.1642C>G
ClinVar accessionVCV003590704
Last evaluated2023/12/27 00:00

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

Full Variant Card

L548V — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Leucine (L) → Valine (V) at position 548 Domain context: Transmembrane helix 8


AlphaMissense

  • Pathogenicity score: 0.2068
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 548: 85.94

DynaMut2 ΔΔG: not yet computed for this variant — AlphaMissense + AlphaFold confidence shown above. Stability ΔΔG and the wild-type/mutant structural comparison backfill behind this note.


Clinical evidence

  • Classification: Uncertain significance
  • Review status: criteria provided, single submitter
  • Associated conditions: Autosomal dominant nonsyndromic hearing loss 6; Cataract 41; Wolfram syndrome 1; Wolfram-like syndrome; Type 2 diabetes mellitus
  • cDNA change: c.1642C>G
  • ClinVar accession: VCV003590704
  • Last evaluated: 2023/12/27 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.612251Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the L548V PDF below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals — guanidinium mimetics, sigma-1 agonist docking, NAC thiol-capping. NAC is already on the bench-testing list.

Download L548V PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.