Sagen JV, et al. - An analysis was designed to compare two families with suspected dominantly inherited diabetes and a new hepatocyte nuclear factor-1A (HNF1A) variant of unknown clinical significance. Evidence suggested that the HNF1A variant p.Ala180Val does not seem to cause MODY3, while it may confer risk for type 2 diabetes mellitus. The outcomes illustrated challenges in causality evaluation of rare variants detected in known diabetes genes.