You could compress the sequences (substrings) into vectors like so: 

my $bitvec = pack "H*", ($string =~ tr/AGCT/1248/r);

[download]
The AGCT values will be interleaved in the resulting bitvector. Better yet, transform the full sequence.

Convert the bitvectors into integer vectors and sum them up. Better yet and if memory allows, create one big vector from the full sequence (with 4*length elements), as the first step.

Then, using an appropriate module with overloading, you might simply (completely untested code): 

my @arrr = split //, unpack "B*", $bitvec;
my $histogram = Math::GSL::Vector->new();
my $sequence = Math::GSL::Vector->new( \@arrr );

while (($pos,$freq) = each %points) {
    my $view = gsl_vector_subvector( $sequence, 4 * $pos, 4 * $slen );

    $histogram += $view * $freq;
    $sum_freq += $freq;
}

# normalize and uninterleave
$histogram *= 1 / $sum_freq;
@parts = part { $i++ % 4 } $histogram->as_list;

[download]
But then, there probably exist specific modules for histogramming...

In reply to Re: Weighted frequency of characters in an array of strings by Anonymous Monk
in thread Weighted frequency of characters in an array of strings by K_Edw

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