The word can have swearing but not genderisation which might be offensive (mother) nor allusions to sexual dominance (motherfucker). Nor, other possibly offensive connotations. It seems that the word is commonplace and people won’t stop using it, so an alternative to the word may be useful. But the problem with alternatives, is that people might not use them unless they carry a meaning that’s attention grabbing in some way, and when it comes to this word it needs to be able to be used in either a serious (non-funny) or comedic way.
I think the more “valued” or preferred part of an insult is rather its phonetic or expressive aspect rather than the semantic one. Of course the semantic parts plays a role, as well, but the need to use stressed syllables to express oneself, or simply vent out the emotion, far surpasses the need to utter a semantically-accurate syllable or word to badmouth someone or something.
See here from Monty Python and the Holy Grail
It is a beautiful insult that can vent out the emotions, or can be used for fun among friends etc. that uses no semantics to insult people, but uses very mouthful words to stress and some unfocused (as in not targeting any types of people) pragmatics, like insulting someone by insulting their parents, and insulting them as such making them out to be not something they are (was an x, smelt).
So, whatever semantically gender-neutral alternative you are looking for, consider to have a very strong expressive aspect to it that sticks to tongue.