First let me say that I understand that this question is best answered by someone familiar with relevant standards (whatever those may be).
Let me give some background. When I'm designing a board at work I usually separate my circuits into several classes. Two of those classes are "signals" and "AC". Nets in the signals class are, e.g., 3.3 or 5 VDC level and may be present on things like user interfaces (the end user doesn't come into direct contact with these nets, but will come closer than to nets in any other class). The AC class contains line voltage nets like 120 or 240 VAC.
For safety we set design rules that say there must be, e.g., 0.250" between nets in the signals class and nets in the AC class. Let's pretend that this clearance is called for by some standard that we would like our products to meet (I don't know if that is true). The nets in the signals class are isolated from nets in AC class by some kind of transformer that can withstand a few kV.
Usually I include the protective earth net in the class AC. This means that signals nets can't come within 0.250" of board mounting points that will be connected to PE.
Now my question. Is this kind of isolation clearance usually required between protective earth and these low level nets? Protective earth is, by definition, accessible to the end user and is considered safe so I see no reason that I would require this large physical isolation distance.
Best Answer
Some I/Os carry a chassis reference by design, so you can't isolate PE from user signals in the general case
Some types of signal connectors (most notably, audio connectors) carry a chassis ground (instead of a signal ground) by design. This is quite important for balanced audio interconnects using TRS or XLR connectors; connecting pin 1 on an XLR or sleeve on a TRS connector to signal ground in an audio application leads to what one calls a "Pin 1 Problem", where noise from the cable shield is injected into the signal reference and thus into the device as a whole.
As a result, it is not possible to maintain a general clearance rule between chassis earth/IO reference earth, which is connected to protective earth given that we are talking about a Class I appliance here, and signals, as your I/O protection and filtering devices will need to be referenced to I/O reference earth as well.