The recent discovery of associations between PLG K330E and ANGPT1 A119S and HAE of unknown genetic cause (HAE-U), has raised the possibility that genetic evaluation could be used to diagnose HAE-U in patients with unexplained angioedema or non-confirmatory laboratory testing.<h4>Case presentation</h4>We analyzed genome sequences from a generally healthy population cohort of 2820 adults and identified PLG K330E in one individual. Here, PLG is linked to angioedema.