This might explain the missing association of LPHN1 variants with obesity and metabolic dysfunctions, e.g., in DisGeNET, a database for gene/variant associations with human diseases.74 In vitro analysis of the two rare variants show that residual receptor activity is retained in both variants, which is in line that complete loss-of-function mutations is not well compatible with healthy life. This evidence concerns the gene ADGRL1 and obesity due to melanocortin 4 receptor deficiency.