Objective: Non-syndromic orofacial cleft (NSOFC), including cleft lip with/or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental aetiological factors. This study investigated the association between (CL±P) and (CP), and two polymorphisms previously determined using GWAS, as well as, the association between consanguinity and (CL±P) and (CP).Methods: DNA using saliva was extracted from 171 affected individuals and 189 control group (age, gender and location) infant-parental triads, recruited from eleven referralhospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located on VAX1 gene were genotyped using real-time polymerase chain reaction (qPCR). A transmission disequilibrium test was carried out using Family Based Association Test and PLINK to measure the parents-of-origin effect.Results: Significant differences were found between affected individuals versus the control group. In the case of rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: