V207F

Category 3/4 — Most DruggableUncertain significanceCytoplasmic · predictedSource card

Valine → Phenylalanine at position 207 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

Interactive 3D Structure

Wild-type reference

Wild-type V207 — hydrogen bond to K186

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DynaMut2 mutant · V207F

Mutant F207 — polar contact to V204 lost (2 contacts lost)

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Bond changes · DynaMut2 interaction analysis

2 lost6 gained7 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	K186	K186	Preserved
Hydrogen bond	V204	V204	Preserved
Polar contact	K186	K186	Preserved
Polar contact	V204	V204	Preserved
Polar contact	G205	G205	Preserved
Van der Waals	—	V204	Gained
Van der Waals	G205	—	Lost
Van der Waals	—	Q226	Gained
Hydrophobic	—	K186	Gained
Hydrophobic	L187	—	Lost
Hydrophobic	—	V204	Gained
Hydrophobic	—	Q226	Gained
Hydrophobic	—	L230	Gained
Hydrophobic	L380	L380	Preserved
Hydrophobic	F384	F384	Preserved

Lost / gained / preserved interatomic contacts at the variant residue, from the DynaMut2 (Arpeggio) interaction analysis of the wild-type and energy-minimized mutant structures.

Computational Predictions

DynaMut2 ΔΔG

-1.14kcal/mol

Destabilising — moderate

AlphaMissense

0.572

likely pathogenic

AlphaFold pLDDT

model confidence

Schema

Cat 3/4

Category 3/4 — Most Druggable

Clinical Evidence

ClinVar classificationUncertain significance

Review statuscriteria provided, single submitter

Associated conditions—

Population frequency (gnomAD v4)Absent from gnomAD v4

cDNA changec.619G>T

ClinVar accessionVCV003605481

Last evaluated2024/08/14 00:00

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

Full Variant Card

WFS1 Wolframin — V207F Variant Card

Molecular Atlas Pilot · RareResearch.AI · Generated by wolfram-variant-card skill

Valine → Phenylalanine at position 207. N-terminal cytoplasmic (intrinsically disordered). ClinVar Uncertain significance, AlphaMissense 0.572, DynaMut2 ΔΔG -1.14 kcal/mol (destabilising).

Identity

Field	Value
Variant	V207F (p.Valine207Phenylalanine)
DNA change	c.619G>T
Gene · Protein	WFS1 · Wolframin (890 aa)
UniProt	O76024 · WFS1_HUMAN
ClinVar accession	VCV003605481
Amino acid change	Valine (V) → Phenylalanine (F)

Structural Context

Field	Value
AlphaFold model	AF-O76024-F1, v6
pLDDT at residue 207	62.16 — confident
Domain	N-terminal cytoplasmic (intrinsically disordered)
Position context	N-terminal cytoplasmic (intrinsically disordered)
IDR flag	No — pLDDT above 50 threshold

UniProt features at this position:

(none catalogued)

Position 207 sits in N-terminal cytoplasmic (intrinsically disordered). The wild-type residue is small hydrophobic (valine — branched); the mutant is large aromatic hydrophobic (phenylalanine). The chemistry shift implies altered local packing, hydrogen-bonding, and/or electrostatics at this site.

Computational Predictions

AlphaMissense

Field	Value
am_pathogenicity	0.5717
am_class	likely pathogenic
Interpretation	Likely pathogenic (threshold 0.564)

DynaMut2

Field	Value
ΔΔG (kcal/mol)	-1.14 (Destabilising)
Job ID	178092134928
Result URL	https://biosig.lab.uq.edu.au/dynamut2/results_prediction/178092134928

Clinical Evidence

Field	Value
Classification	Uncertain significance
Review status	criteria provided, single submitter
Last evaluated	2024/08/14 00:00
Inheritance	Inheritance pattern not specified in ClinVar entry; WFS1 has both AD and AR presentations.
WFS1 variant landscape	V207F is 1 of ~326 pathogenic-spectrum variants in WFS1 (out of 2,243 catalogued in ClinVar)

(no conditions catalogued)

Research Path Decision Tree

ΔΔG < 2  + binding site affected   →  CATEGORY 3 — docking experiments
ΔΔG 2–4                            →  CATEGORY 2 — pharmacological chaperones
ΔΔG > 4                            →  CATEGORY 1 — gene therapy
pLDDT < 50                         →  CATEGORY 5 — IDR, experimental only
Stable fold + functional site hit  →  CATEGORY 4 — site-specific docking

Final Schema Categorization

Category 3/4 — Most Druggable

<strong>Category 3/4 — Most Druggable</strong><br/><br/>|ΔΔG|=1.14 < 2 kcal/mol (fold intact) + AlphaMissense 0.572 confirms functional impact. Specific local contacts disrupted — priority for docking and pharmacological chaperone screening.

Why this card matters. Wolframin's fold survives this substitution (|ΔΔG|=1.14 kcal/mol). The pathogenic signal is real — AlphaMissense places it at 0.572. Protein still folds, but a specific local site is broken. Pharmacological chaperones and small-molecule binders are the rational therapeutic vector.

Files in this folder

AF-O76024-F1-model_v6.pdb — AlphaFold structure
V207F_molstar_viewer.html — interactive 3D viewer (auto-highlights position 207 with ball-and-stick + neighbors within 5Å)
V207F_variant_card.md — this card (source of truth)
V207F_variant_card.html — styled printable card
V207F_dynamut2_summary.html — clean offline DynaMut2 result card
dynamut2_result.json — structured result data
dynamut2_result_page.html — local snapshot of the Biosig result page (asset URLs absolutized)
V207F_wildtype_interactions.pse / V207F_mutant_interactions.pse — PyMOL sessions

Generated by wolfram-variant-card skill · RareResearch.AI Molecular Atlas Every assumption documented. Every score sourced.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the V207F 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 V207F PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.