ARR4 has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES) in a Southern Chinese family, we identified the first hemizygous high myopia case in a male patient. A novel truncated mutation (ARR4: c.569C>G, p.S190*), which co-segregated with the disease phenotype in affected members, was identified in this family. Because the proband’s father was a hemizygote for the ARR4 variant, the present study demonstrated a case where high myopia caused by ARR4 is not X-linked, female-limited. This implied that a complicated X-linked inheritance pattern may exist for ARR4. Thus, the results of this study expanded the variant spectrum in ARR4 and provided additional information for genetic counseling, prenatal testing and diagnosis. Moreover, we characterized the pathogenic role of ARR4 c.569C>G (p.S190*) and demonstrated that the mutant protein accumulated under ER stress and was degraded by the proteasome.