Early evidence seems to show that AlphaFold has trouble with single point mutations that change a protein's shape, so completely de-novo proteins will be a challenge:
Fortunately, evolution already encoded robustness against this sort of problem into proteins and the vast majority of single point mutations are tolerated (the resulting enzymes are often nearly as active and stable as the originals).
Don't forget that you can replace the three residues in the serine protease catalytic triad and still see significant proteolytic activity. Everything we know about protein activity is wrong.