The article is a response to a comment on a previous study about predicting the pathogenicity of variants in ion channels. The authors of the response acknowledge that their cross-channel approach may not be accurate for all families of ion channels due to their structural and functional differences. They suggest that a protein-specific approach, tailored to the structure and activation mechanism of each ion channel, may be more effective. The response highlights the merits of this approach, including the need for clinical-grade accuracy, consideration of protein dynamics, and the refinement of predictive features. The study by Absalom et al. demonstrates the potential of a protein-specific approach to improve variant classification and deepen our understanding of biological functions. [Extracted from the article]