In this study, the effect of local site conditions (site class and site amplifications) and structural variability are investigated on fragility functions of typical building structures. The study area is chosen as Eastern Turkey. The fragility functions are developed using site-specific uniform hazard spectrum (UHS). The site-specific UHS is obtained based on simulated ground motions. The implementation of ground motion simulation into seismic hazard assessment has the advantage of investigating detailed local site effects. The typical residential buildings in Erzincan are represented by equivalent single degree of freedom systems (ESDOFs). Predictive equations are accomplished for structural seismic demands of ESDOFs to derive fragility functions in a straightforward manner. To study the sensitivity of fragility curves to site class, two sites on soft and stiff soil are taken into account. Two alternative site amplification functions known as generic and theoretical site amplifications are examined for these two sites. The reinforced concrete frames located on soft soil display larger fragilities than those on stiff soil. Theoretical site amplification mostly leads to larger fragilities than generic site amplification more evidently for reinforced concrete buildings. Additionally, structural variability of ESDOFs is generally observed to increase the fragility especially for rigid structural models.