As CES drivers are frequently involved in severe diseases, the GoF-like 500-fold elevation in mutation rate might generate a substantial rate of de novo pathogenic mutations, e.g. is the same inflation was present for LoF mutations in ARID1B, about 0.5% of all individuals would be born with NDD if the CES effect was so high. The gene discussed is ARID1B; the disease is Neurodevelopmental delay.