Why not positional variation?

[ReneZ]

It is easy to show that the MS is certainly not any straightforward substitution.
If there is any substitution from a plain text involved, the best candidate is a verbose substitution.
This means that one PT character is represented as a (short) string of Voynich glyphs.
For that to work, we need (as one option) a small set of Voynich characters.

So, indeed, I do not see that as an issue at all.
Of course, all this is hypothesis, to be confirmed by some tangible result.