In this work, a novel Fréchet-derivative-based global sensitivity analysis is incorporated into the probability density evolution method for the simultaneous reliability and sensitivity analysis of structures. The two methods are synthesized and realized under a two-stage uncertainty quantification framework. Fundamental and numerical algorithms of the method are described, which is validated by a benchmark problem with theoretical solutions. Then it is applied on studying stochastic seismic responses of a real-world reinforced concrete structure of 288 m high. Results demonstrate that the response characteristics of the structure will be greatly changed when both uncertainties from the ground motions and structural parameters are considered, e.g., the failure probability will be enlarged by 1∼2 orders of magnitude. Besides, contrary to the popular opinion that the uncertainty of structural parameters is trivial compared to that of parameters in the ground-motion model, the importance measures of the structural parameters can be greater than those of the parameters in the ground-motion model by a factor of 2. when the coupling effect of randomness and nonlinearity of structural materials becomes dramatic. Some issues to be further outlined are also discussed.