Does this truncating variant remove a functional protein domain?

Figure: illustrative, generated to demonstrate the method

The question

Does the candidate stop-gain alter only the protein length, or does it remove a structured region needed for the protein’s proposed function?

Two predicted protein structures side by side; the truncated model lacks the C-terminal domain present in the wild-type model. — Predicted structures of the wild-type protein and the truncated product shown side by side, with the lost C-terminal domain and its mapped interface residues highlighted.

Method

Sequence reference: MANE Select transcript
Model: AlphaFold 3 prediction
Domain mapping: InterPro release 101.0
Review: per-residue confidence, domain boundaries, and interface residues

What the figure shows

The predicted upstream fold is retained, while the truncation removes the C-terminal domain and several mapped interface residues. Confidence near the new terminus is lower and is not interpreted as a stable novel fold.

What follows from it

The variant is predicted to cause domain loss rather than a local structural substitution. A simple surface-residue effect and a preserved complete domain were considered and ruled out by the sequence boundary; experimental functional testing is still required.

This analysis is what a target tractability assessment delivers.