According to Human Gene Mutation Database (HGMD) Professional 2021.2, five missense variants associated with autism (Sanders et al., 2012; Kosmicki et al., 2017; Satterstrom et al., 2020), cerebral palsy (McMichael et al., 2015), and congenital heart defect (Jin et al., 2017) have already been reported in RFX2. Here we report a novel sequence variant c.1421T > C; p.(Ile474Thr) in this gene in an autosomal recessive family exhibiting tooth agenesis. The gene discussed is RFX2; the disease is tooth agenesis.