Discussion Predicting the 3D structure that a protein will assume based solely on its amino acid sequence has been a significant challenge in research for over 50 years (Anfinsen, 1973; Dill et al., 2008). A recent study has revealed the molecular effect of missense variants by accomplishing a comprehensive characterization of amino acid positions in protein structures, providing reference for the clinical interpretation of pathogenic and benign missense variants (Iqbal et al., 2020).
