Some more experiments, comparing an installed vs uninstalled Python. One failure mode is that setting PYTHONHOME just plain breaks running from a source checkout (setting PYTHONHOME to the checkout directory also fails):

$ ./python -m venv --without-pip /tmp/issue22213-py35

$ /tmp/issue22213-py35/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
/usr/local /usr/local

$ PYTHONHOME=/usr/local /tmp/issue22213-py35/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
Fatal Python error: Py_Initialize: Unable to get the locale encoding
ImportError: No module named 'encodings'
Aborted (core dumped)

Trying after running "make altinstall" (which I had previously done for 3.4) is a bit more enlightening:

$ python3.4 -m venv --without-pip /tmp/issue22213-py34

$ /tmp/issue22213-py34/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
/usr/local /usr/local

$ PYTHONHOME=/usr/local /tmp/issue22213-py34/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
/usr/local /usr/local

$ PYTHONHOME=/tmp/issue22213-py34 /tmp/issue22213-py34/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
Fatal Python error: Py_Initialize: Unable to get the locale encoding
ImportError: No module named 'encodings'
Aborted (core dumped)

$ PYTHONHOME=/tmp/issue22213-py34:/usr/local /tmp/issue22213-py34/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
Fatal Python error: Py_Initialize: Unable to get the locale encoding
ImportError: No module named 'encodings'
Aborted (core dumped)
[ncoghlan@lancre py34]$ PYTHONHOME=/usr/local:/tmp/issue22213-py34/bin /tmp/issue22213-py34/bin/python -c "import sys; print(sys.base_prefix, sys.base_exec_prefix)"
/usr/local /tmp/issue22213-py34/bin

I think what this is actually showing is that there's a fundamental conflict between mod_wsgi's expectation of being able to set PYTHONHOME to point to the virtual environment, and the way PEP 405 virtual environments actually work.

With PEP 405, all the operations in getpath.c expect to execute while pointing to the *base* environment: where the standard library lives. It is then up to site.py to later adjust the based prefix location, as can be demonstrated by the fact pyvenv.cfg isn't processed if processing the site module is disabled:

$ /tmp/issue22213-py34/bin/python -c "import sys; print(sys.prefix, sys.exec_prefix)"
/tmp/issue22213-py34 /tmp/issue22213-py34
$ /tmp/issue22213-py34/bin/python -S -c "import sys; print(sys.prefix, sys.exec_prefix)"
/usr/local /usr/local

At this point in time, there isn't an easy way for an embedding application to say "here's the standard library, here's the virtual environment with user packages" - it's necessary to just override the path calculations entirely.

Allowing that kind of more granular configuration is one of the design goals of PEP 432, so adding that as a dependency here.