Generalized vitiligo is a common autoimmune disorder, characterized by patchy loss of pigmentation due to melanocyte death. It is a multifactorial disorder in which multiple genes and environmental triggers contribute to the expression of the phenotype. Different genetic variants can have varying effects on having vitiligo. Recently, an SMOC2 variant (rs13208776) was reported to be associated with vitiligo in Caucasian patients from an isolated founder population. In this study, we investigate the association of SMOC2 variant with Jordanian Arab vitiligo patients. Forty-four patients with generalized vitiligo and 151 matched normal controls were recruited. DNA samples were obtained from patients and controls and samples were genotyped for SMOC2 variant by restriction fragment length polymorphism. Allelic frequency of the less common allele (A allele) was 29.5% in patients compared to 19.6% in the controls (p = 0.27). Genotypic frequency for AA was 4.5% in patients and 7.9% in controls while heterozygous genotypes were 50% for patients and 33.1% in controls. Genotypes did not show statistical difference in patients versus control (p = 0.12). Our data shows that the variant rs13208776 in SMOC2 gene does not play a major role in increasing the risk of vitiligo in Jordanian Arab patients. This is in contrast to the previous association reported for Caucasian patients from an isolated patient population in Romania. This signifies genetic differences in the two populations.