Supposing that is true, how does that rule it out? If we put that into the argument, the conclusion still doesn’t follow, or is it even implied.
Premise 1: PRPF8 is highly conserved. Check!
Premise 2: Sequence space for proteins of that length is 20^L, which is a very large number. Check!
Premise 3: The total number of functional sequences is less than the total sequence space. Check!
Premise 4: There is no evidence of lower fitness PRPF8 alleles.
Conclusion: Therefore it is highly doubtful, or impossible, that PRPF8 could have evolved.
Still an invalid argument. The conclusion of that argument still does not follow from those premises.