Can a mistake be so big, that the one who did will never have your respect again?

[Der/die AtheistIn]

For me "mistake" implies that the other party did whatever they did unknowingly and so I wouldn't hold it against them for long, irrespective of the consequence, provided once they realise their mistake they at least try to make amends for it!

I'd say the golden rule applies here too, put yourself in their shoes and think, if you'd have done that mistake would you want the other side to hold against you or give you a chance to make amends?

If the mistake I did was really stupid, if it had all the criterias I listed in the OP and to a very high level I don't think I would see myself as worthy of forgiveness.