§ 25.365 Pressurized compartment loads.
For airplanes with one or more pressurized compartments the following apply:
(a) The airplane structure must be strong enough to withstand the flight loads combined with pressure differential loads from zero up to the maximum relief valve setting.
......
(d) The airplane structure must be designed to be able to withstand the pressure differential loads corresponding to the maximum relief valve setting multiplied by a factor of 1.33 for airplanes to be approved for operation to 45,000 feet or by a factor of 1.67 for airplanes to be approved for operation above 45,000 feet, omitting other loads.
So your minimum margin is either "flight loads plus nominal pressurisation" or a factor (usually 1.33) times nominal pressurisation.