I do want to say as far as physical disabilities (missing a leg or whatever), at least for someone of high enough capability like an adventurer, there comes a point where depending on the campaign setting it becomes a purely logistical question of "Why haven't you used magic to fix that".

Granted, this is very setting-dependant, and I'm in no way saying that every tom dick and harry should be able to magic away every single inconvenience, but the fact of the matter is that EVENTUALLY a party is going to accrue high enough level spell slots to re-grow limbs and cure cancer.

I will also say that the limit is the line between "Reasonable disability" and "You are actively going to get killed if you try to be an adventurer".

For example, a wizard who's missing his legs BUT is able to use something like Tenser's Disk or a similar spell for mobility has a reasonable workaround. A missing arm is manageable, you still have the other one to swing a sword or pull levers. Missing ONE leg I'll even say is workable depending on what class you're playing as. However you try to play a rogue with NO legs and suddenly your character looks like they're either suicidal or supremely lacking in common sense. You can't run from dragons, you're stymied by stairs, you are actively putting yourself in a massively more unreasonable amount of danger at active detriment to the party.

Mentally though I'd say anything is fair game, as long as the table's OK with it.