You want to use a negative look-ahead assertion (as described in 'perlre'):

$string = "123456123789";
$a = 123;
$b = "abc";
$c = 456;
$string =~ s/$a(?!=$c)/$b/;
[download]

That sets string to "123456abc789". (?=...) is a positive look-ahead, (?!=...) is a negative look-ahead. (?<=...) is a positive look-behind, (?<!...) is a negative look-behind.