This study defines the most comprehensive CYP17A1 variant spectrum for complete 17-OHD in China, identifies 6 novel pathogenic variants, and uncovers splicing disruption as an under-recognized mechanism in missense mutations. These findings expand the molecular and clinical understanding of 17-OHD, highlight the founder effect of c.985_987delinsAA in the Chinese population, and provide critical insights for genetic diagnosis and counseling.