It's when the dry part of the effect signal is digitized. This can't be done without 'latency' (a very short delay basically, usually a mS or so), so when you mix that with the undelayed dry signal in the amp you get essentially a stuck flanger.
It can also happen if the dry part of the effect is reverse-phased - this can happen even with some analog pedals, and I notice you also have a Phase 90 which is one of them! Not because it's a 'phaser', but because the polarity of the dry signal is inverted at some part of the audio path in it. The effect this time is more like a stuck phaser. (You may be running this in front of the amp, so no problem.)
If you're really unlucky you might have both problems at the same time, or even the third one which is feedback via the mix pot, which tends to sound more like a stuck ring modulator.
A series loop doesn't suffer from any of these problems - and nor does a parallel one if it's done properly so the two signals are independent and you can turn the mix to truly 100% wet. The problem is that the Mesa loop is very crude and the same single pot is used to mix both signals, so they bleed into each other even when the pot is set to full up or full down.
