Protein SAE Variant Interpretation

Interpret a single missense variant by comparing reference vs mutant Sparse Autoencoder (SAE) feature activations from the ESMC-6B protein language model. SAE features are interpretable latent dimensions of the model's hidden state — many activate on biologically meaningful patterns (active sites, ligand-binding pockets, PTM sequons, structural motifs).

When to use this skill

Apply when users:

• Ask "why is variant X (a missense) loss-of-function?" and need a mechanistic answer beyond a pathogenicity score
• Have an AlphaMissense / ClinVar "damaging" variant and want to know which functional feature breaks (catalytic? binding? PTM site? structural?)
• Want to compare ref vs mutant protein representation at a specific residue
• Are interpreting why a structurally subtle change (single AA) has a big functional impact

Not for (use other skills instead):

• ACMG pathogenicity classification → tooluniverse-variant-interpretation
• Regulatory / non-coding variants → tooluniverse-variant-to-mechanism
• Variant-to-disease association without mechanism → tooluniverse-gene-disease-association
• Cancer-specific variant interpretation → tooluniverse-cancer-variant-interpretation