Originally Posted by Skatering

I mean, hypothetically no, but I guess people could be rejected under the catch-all of 'cannot satisfy us of low-risk status'.

My transgender status is always sitting in the background of applications, but it seldom even comes up. CBP never mentioned it for my Global Entry interview. Canadian visa officer I was interviewed by asked one question about it but really couldn't care less.

If people have personal prejudices against transgender people, they often don't manifest themselves when they meet one in the flesh and realise we're pretty normal people.