Reinforced Concrete (RC) buildings are the most common type of construction typology existing worldwide. RC buildings with masonry infill walls have undergone varying degree of damage during past earthquakes; therefore, seismic fragility assessment of such buildings becomes necessary to predict its damageability. RC frames with irregular distribution of infills are seismically even more vulnerable. For example, open ground story buildings are vertically irregular buildings with no infills in the ground story. As discussed later, such buildings undergo large lateral deformation in the ground story, resulting in excessive ductility demand from ground story columns leading to their eventual failure. The present study investigates the existing seismic fragility assessment methodologies with respect to different engineering demand parameters (EDPs) for RC frames with and without vertical irregularities (soft story effect). EDPs are structural response quantities that can be used to predict damage to structural and nonstructural components and systems [Whittaker et al., 2004]. The most common global EDP considered in a large scale fragility assessment of building stock includes peak roof or top story displacement or maximum inter-story drift over the height of the building. Here, the global displacement or drift response of the building is entirely defined by the top story displacement assuming the first modal displacement pattern as dominant. However, such a methodology is insufficient to describe exactly the failure mechanism in buildings, particularly in case of irregular frames, such as open ground story (OGS) frames, where the failure is mostly concentrated at the level of irregularity. OGS columns lack adequate ductility capacity, stiffness, and strength needed to resist the high demand of story shear. This leads to an undesirable column-sway failure mechanism in OGS buildings subjected to earthquake excitations, in which failure occurs mostly in the columns of the ground story. In contrast, the infills present in the upper stories restrain the deformation of the upper story, and thus, little damage is incurred in the upper storys of such buildings. The vulnerability of the open ground story frames was observed by Mondal and Tesfamariam [2014] who reported that the infill thickness and vertical irregularity have significant influence on the response of RC frames. Similarly, the higher seismic vulnerability of vertically irregular masonry infilled frames was also observed in several past studies [e.g., Dolšek and Fajfar, 2001; Yuen and Kuang, 2015; Choudhury and Kaushik, 2018; Aschheim et al., 2000; Kaushik and Jain, 2007].