Because the Mapk1A172V pathogenic variant near the ERK2 activation domain increased kinase activity, we were able to address an important unanswered question in the Rasopathy field: to what extent do mice with gain-of-function mutations in downstream Ras effectors, like the terminal MAP kinase ERK, genocopy Rasopathy model mice with genetic perturbations acting upstream or at the level of Ras? The gene discussed is MAPK1; the disease is RASopathy.