Documentation

Input and output reference

This resource accepts human protein missense variants and returns mechanistic annotations derived from sequence-based and structure-based prediction.

The documentation below defines the expected input format and the main output fields shown in the interface.

Input format

Queries use protein-level missense notation in the form:

UNIPROT_ID/REFPOSALT

Example:

Q7Z4H8/A126C

This represents a substitution in protein Q7Z4H8 at residue 126 from alanine (A) to cysteine (C).

Multiple variants can be submitted together, one per line.

Supported query type

This site is designed for human protein missense variants.

The expected identifier is a UniProt accession paired with a single amino acid substitution. Other variant types, transcript notations, genomic coordinates, insertions, deletions, and synonymous changes may not be supported in the main search interface.

Output fields

variant_id

Protein variant identifier in the form UNIPROT_ID/REFPOSALT.

Example: Q7Z4H8/A126C

am_pathogenicity

AlphaMissense pathogenicity probability, ranging from 0 to 1.

Higher values indicate stronger predicted support for a deleterious functional effect.

am_class

Discrete AlphaMissense class.

Expected values are:

  • pathogenic
  • ambiguous
  • benign

am_label

Boolean AlphaMissense pathogenicity label.

Expected values are True or False.

ESM1b_LLR

ESM1b likelihood-related score.

Lower values indicate stronger support for a deleterious effect.

ESM1b_is_pathogenic

Boolean ESM1b pathogenicity label.

Expected values are True or False.

pred_ddg

Predicted change in protein stability as ΔΔG.

Higher positive values indicate stronger predicted destabilisation. Values near zero suggest limited predicted stability impact.

pred_ddg_label

Boolean stability label derived from the ΔΔG prediction.

Expected values are True or False, where True indicates predicted destabilisation according to the applied threshold.

interface_pdockq

Confidence score for a predicted protein-protein interaction model, where available.

Higher values indicate greater confidence in the predicted interface model.

interface_label

Boolean interface annotation.

True indicates that the residue is annotated as lying in a predicted protein-protein interface.

pocket_label

Boolean pocket annotation.

True indicates that the residue is annotated as lying in a predicted small-molecule binding pocket.

mechanistic_label

Summary mechanism label derived from the available structural annotations.

Expected values include:

  • Unassigned
  • Stability
  • Pockets
  • Interface

How to read a result

The fields are designed to be interpreted together.

A high AlphaMissense score suggests likely functional disruption. The structural annotations indicate whether that disruption is more consistent with instability, a protein-protein interface, or a binding pocket.

Not every variant will receive a mechanism label. Unassigned means that no specific structural mechanism could be assigned from the available annotations.

Example

Input

Q7Z4H8/A126C

Interpretation

A result with high am_pathogenicity, a positive destabilising pred_ddg, and mechanistic_label = Stability suggests that the variant may disrupt function through reduced structural stability.

A result with high pathogenicity but interface_label = True and mechanistic_label = Interface suggests that altered interaction surfaces may be the more relevant mechanism.

Scope

This resource is intended for mechanistic annotation of human missense variants.

It does not call variants, assign clinical pathogenicity, or replace experimental validation.