RareResearch.AI
← Back to atlas

V415L

AlphaMissense: likely benign (0.32)Uncertain significanceTransmembrane · predicted
Valine → Leucine at position 415 · Transmembrane helix 4 · WFS1 (Wolframin)

Interactive 3D Structure

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

Computational Predictions

AlphaMissense
0.317
likely benign
AlphaFold pLDDT
93
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, multiple submitters, no conflicts
Associated conditionsCataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome
Population frequency (gnomAD v4)Ultra-rare · AF 0.0018%
cDNA changec.1243G>C
ClinVar accessionVCV001370377
Last evaluated2025/12/22 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

V415L — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Valine (V) → Leucine (L) at position 415 Domain context: Transmembrane helix 4

AlphaMissense

  • Pathogenicity score: 0.3172
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 415: 93.25

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, multiple submitters, no conflicts
  • Associated conditions: Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome
  • cDNA change: c.1243G>C
  • ClinVar accession: VCV001370377
  • Last evaluated: 2025/12/22 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.519727Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the V415L 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 V415L PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.