Although Cyrus offers best-in-class protein design, there are limits to what it is recommended to attempt. As seen in this question it is possible to redesign 20% or more of a sequence, but it requires many cycles with separate tools, not a single run through Design. This is an inherently hard experiment that Cyrus Biotechnology has made easy to perform: be careful that the ease of selecting mutations does not tempt you to try too many at a time.
The red flags that your design problem requires more computational confirmation (detailed above) are if:
1.) You are designing more than a handful of point mutations
2.) You are designing neighboring residues (in either sequence or Cartesian space)
The most conservative route would be to break your design problem into as many small Design operations as possible, verifying their success in-between with the other Bench tools. ‘