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The seismic protection of small and medium historical towns is an important and current issue in Italy and in many other earthquake prone regions of Europe, where seismic actions are generally responsible for severe damages and collapses of buildings. In this context, the seismic vulnerability assessment of unreinforced masonry buildings assumes a crucial role considering the fact that they represent a widespread construction typology in Italian and European towns. Among the various approaches to evaluate the seismic vulnerability of existing buildings, fragility curves represent a very effective one in predicting potential damages of geographical areas characterized by similar building typologies. This paper presents the evaluation of fragility curves for macro-typologies of masonry buildings representative of a specific regional area in Italy and prone to the occurrence of out-of-plane collapse mechanisms in case of seismic events. In order to obtain consistent fragility curves, virtual populations of buildings are generated starting from the buildings of a selected case study, the Borgo San Rocco in Sora (FR).