It's not very subtle. I just whipped together an example[1]. Note that I had to take a photo of the screen with my phone to show what the screen is actually displaying.
F.lux doesn't "deal" with anything, it just takes your existing ICC/ICM file, alters it, and resets your GPU's LUT with it.
I've had the same issue with an Intel GPU'ed MBPR 13" (ie, no Radeon or Nvidia GPU also), and it rarely happened in OSX, but only during certain HW accelerated overlays (such as YUV acceleration in videos, or OpenGL programs doing sufficiently interesting things).
I don't think F.lux has the bug, but OSX's rendering pipeline does. I had similar issues with color profiles I generated myself that noticeably differed from the screen itself (Apple has yet to produce an actually fucking accurate-to-sRGB screen, I don't care how many Photoshop jockeys praise their lord and savior, St. Jobs).
So, yeah. In other news, my MBPr runs Windows 10 and I'm never going back; and I've also never seen the bug here.
The side effect is: F.lux's Windows version is not feature complete with OSX's, and noticeably redshifts at different times than OSX does depending on what settings you prefer.
