To evaluate the kinematic performance of designed mechanisms, a statistical-variance-based metric is proposed in this article to measure the “distance” between two discrete motion sequences: the reference motion and the given task motion. It seeks to establish a metric that is independent of the choice of the fixed frame or moving frame. Quaternions are adopted to represent the rotational part of a spatial pose, and the variance of the set of relative displacements is computed to reflect the difference between two sequences. With this variance-based metric formulation, we show that the comparison results of two spatial discrete motions are not affected by the choice of frames. Both theoretical demonstration and computational example are presented to support this conclusion. In addition, since the deviation error between the task motion and the synthesized motion measured with this metric is independent of the location of frames, those corresponding parameters could be excluded from the optimization algorithm formulated with our frame-independent metric in kinematic synthesis of mechanisms, and the complexity of the algorithm are hereby reduced. An application of a four-bar linkage synthesis problem is presented to illustrate the advantage of the proposed metric.