The study of metal-insulator transitions in crystalline solids is a subject of paramount importance, both from the fundamental point of view and for its relevance to the transport properties of materials. Recently, a metal-insulator transition governed by disorder was observed in crystalline phase-change materials. Here we report on calculations employing Density Functional Theory, which identify the microscopic mechanism that localizes the wave functions and is driving this transition. We show that, in the insulating phase, the electronic states responsible for charge transport are localized inside regions having large vacancy concentrations. The transition to the metallic state is driven by the dissolution of these vacancy clusters and the formation of ordered vacancy layers. These results provide important insights on controlling the wave function localization, which should help to develop conceptually new devices based on multiple resistance states.