A specific trait of one-hot encoded protein descriptors is that every feature can be traced back to specific protein sequence residues or MSA positions. For class A GPCRs, the aligned positions can additionally be linked to generic positions in the GPCR structure with known functional relevance. The most widely used generic position identifier for class A GPCRs is the Ballesteros-Weinstein (BW) schema , which consists of a first number identifying the TM domain followed by a second number that represents the level of conservation in that helix around the most conserved position that gets the value 50. Using the GPCRdb MSA mapping to BW positions, the most important rs3DDPD features in regression models were traced back to their generic GPCR positions. In the models built with a temporal split, four rs3DDPD features were among the top 25 most important (Figure ). The most important feature overall, AA223_PC3, corresponded to the BW position 3.32 in TM3. For further interpretability, this generic position can also be directly mapped to a specific residue in a protein of interest. As an example, in AA1R 3.32 translated to Val 87 (Figure ). The other three important rs3DDPD features did not correspond to any BW positions, as two of them were located in the ECL2 and one in the ECL3. From the three loop positions, only one exists in adenosine receptor A1, Asn 147 (AA292_PC3). The two other ECL positions are only available in other receptors (Figure ).