I shared the same concerns and then realised that I only ever play one song that uses the 22nd fret! I've got a gorgeous AV52RI Telecaster that has 21 frets and I don't miss the extra one that my strat and LP have got.
You'll notice it at first if you're into lead playing, then you get used to it. But then you'll play one of your other guitars and find yourself running up to that 22nd fret a bit excessively simply because you can. Then you'll be over it. And if you are super loud and playing with distortion you can make that high D sound on the 21 fret neck if you want it bad enough (sort of like a fretless bass or violin).
I would buy the guitar for what it is. A good guitar is a good guitar regardless of number of frerts. If it speaks to you, buy it for what it is.
As for how often do one uses the 22nd fret, I do need it here and there. A lot of times it's for bending notes though. It's much easier to bend 3 steps up from the 22nd fret than bending 4 steps up from the 21st.
on the one hand, how often do you use that extra fret? but when you want to use it, would you rather it be there. it doesnt bother me to own a 21 fret strat, but every once and a while im going off and i find myself running out of room, i wish i had more frets, but not enough to do anything about it. its a very subjective/personal thing