Because DNA methylation is a major mechanism of tissue-specific gene silencing and given that CGIs are discrete CpG-rich regions in 50–70% of human gene promoters21, we analyzed bona fide CGIs in Ccer1 and found that they were hypermethylated in normal somatic tissues but not in germ cells, explaining the germline-specific expression of Ccer1. Our findings showing that heterozygous human CCER1 variants are pathogenic in patients with clinical azoospermia were supported by highly significant differences in our large-cohort study. The gene discussed is CCER1; the disease is Azoospermia.