Yes...
No!
Wrong.
It's not an issue for the first release of a game, but for it only.
For any following release, either the code is kept clear and organized, with all variables declaration being grouped in the "start" label, and therefore the game will not be save compatible. Or the game is kept save compatible, and therefore the variables declaration will be spread all over the code, what is the opposite of "clear and organized".
And, obviously, doing it for the very first release is also not an option, because it starts a bad habit.
Ren'Py have two statements specially dedicated to variables declarations, and every devs should use them. The first one being
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d as constants, and the second being
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for all the other variables.
This is
the only way to have both a clear and organized code, and a save compatible game (at least when it come to variables). All declarations are located in the same place, by example a loose file like Winterfire said. This while ensuring that all variables will exist in a players play, whatever the moment they've been added to the game, whatever how old the save file is, and whatever content the player have seen during his own playthrough.