One consequence of the continued downward scaling of transistors is the reliance on only a few discrete atoms to dope the channel, and random fluctuations in the number of these dopants are already a major issue in the microelectronics industry(1). Although single dopant signatures have been observed at low temperatures(2-8), the impact on transistor performance of a single dopant atom at room temperature is not well understood. Here, we show that a single arsenic dopant atom dramatically affects the off-state room-temperature behaviour of a short-channel field-effect transistor fabricated with standard microelectronics processes. The ionization energy of the dopant is measured to be much larger than it is in bulk, due to its proximity to the buried oxide(9,10), and this explains the large current below threshold and large variability in ultra-scaled transistors. The results also suggest a path to incorporating quantum functionalities into silicon CMOS devices through manipulation of single donor orbitals.