Trans!Regulus makes makes sense to me for a few reasons, honestly.
For one, it explains why it took so long for Sirius to be disowned. We know that the House of Black had very old values, so I can picture them not being accepting of trans people and not wanting a “woman” to be in charge. We know they disowned easily— think about Alphard— but they didn’t get rid of Sirius until he ran away. I could picture them keeping Sirius around to try and have a viable heir.
For two, it would give motivation for Regulus to rethink things. In the end, he did betray Voldemort, but, before that, he was wholly devoted to the cause. Maybe the reason he rethought things is because he realized he didn’t fit the mold, causing him to ask questions, before he figured it out and backtracked.
For three, I just like trans characters. Fuck JKR, she deserves to be pissed off by us making characters trans. I’d make Regulus trans if only to make her upset.