As strings are immutable in Python, just create a new string which includes the value at the desired index.

Assuming you have a string s, perhaps s = "mystring"

You can quickly (and obviously) replace a portion at a desired index by placing it between "slices" of the original.

s = s[:index] + newstring + s[index + 1:]

You can find the middle by dividing your string length by 2 len(s)/2

If you're getting mystery inputs, you should take care to handle indices outside the expected range

def replacer(s, newstring, index, nofail=False):
    # raise an error if index is outside of the string
    if not nofail and index not in range(len(s)):
        raise ValueError("index outside given string")

    # if not erroring, but the index is still not in the correct range..
    if index < 0:  # add it to the beginning
        return newstring + s
    if index > len(s):  # add it to the end
        return s + newstring

    # insert the new string between "slices" of the original
    return s[:index] + newstring + s[index + 1:]

This will work as

replacer("mystring", "12", 4)
'myst12ing'

you can do

s="cdabcjkewabcef"
snew="".join((s[:9],"###",s[12:]))

which should be faster than joining like snew=s[:9]+"###"+s[12:] on large strings

The problem is that .replace(old, new) returns a copy of the string in which the occurrences of old have been replaced with new.

Instead, you can swap the character at index i using:

new_str = old_str[:i] + "b" + old_str[i+1:]