This may be overkill, but here's an approach to controlling which of several parenthesized digit groups gets its digits quoted (requires  \K from 5.10):

use warnings;
use strict;

my $paren_grp = qr{ \( \d+ (?: , \d+)* \) }xms;
my $non_paren = qr{ [^(] }xms;

for my $n (0 .. 3) {
    my $s = '(1) XXX (123) YY YY (1,22,333) Z Z Z (22,1)';
    $s =~ m{ \A $non_paren* (?: $paren_grp $non_paren*){$n} \( }xmsg;
    $s =~ s{ \G ,? \K (\d+) }{'$1'}xmsg;
    print qq{skip $n  :$s: \n};
    }
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Output:

skip 0  :('1') XXX (123) YY YY (1,22,333) Z Z Z (22,1):
skip 1  :(1) XXX ('123') YY YY (1,22,333) Z Z Z (22,1):
skip 2  :(1) XXX (123) YY YY ('1','22','333') Z Z Z (22,1):
skip 3  :(1) XXX (123) YY YY (1,22,333) Z Z Z ('22','1'):
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Update: I think it should be possible to integrate the two-step  m//g; s///g; approach entirely into a single  s///g; regex (possibly using 5.10's backtracking control verbs), but I can't quite figure out how – and I'm not sure it would be worth the effort except to satisfy my curiosity!