In terms of variant clinical interpretation, as most PTVs lead to reduced SorLA levels through nonsense-mediated decay (NMD) [22, 23, 26] and/or to the putative production of truncated proteins and hence increased Aβ production, one could consider that most PTVs are likely strong AD risk factors in case they are to be used in a clinical setting. The gene discussed is SORL1; the disease is Alzheimer disease.