Tubulin beta 8 class VII (TUBB8), a primate oocyte/embryo-specific β-tubulin isotype, is a preferentially analyzed gene in the genetic diagnosis of infertile women. Studies have currently identified 47 variants of this gene. However, the evaluation of its pathogenicity and the resulting phenotypes vary, and this gene requires further study in order to be included in genetic counseling analyses. We have performed a whole exome sequencing (WES) screening of 385 infertile female subjects and 400 controls, identifying 29 TUBB8 variants (of which 23 were novel). These variants may be responsible for female infertility, especially in the case of embryonic arrest, and their identification further expands the variant spectrum of TUBB8. Our findings are the first to report a new phenotype of large polar body in TUBB8 variant patients and determine some recurrent variants that were specific for complete cleavage failure. We have also illustrated some phenotypes of TUBB8 variant patients and recommended using computational modeling approach to assess the pathogenicity of novel TUBB8 variants, particularly for maternally inherited variants. Our studies will contribute in laying the foundation for the genetic counseling of infertile women in the future.