The average reconstruction accuracy of the sequence was approximated as an average reconstructed sequence identity for 5,000 samples around the original sequence coordinates of its latent space embedding. The parameters of sample distribution are determined by the encoder (mean, variance) for a given sequence. The negative control subset was generated by sampling sequences from the profile of input MSA only based on the amino acid frequencies in each position. The positive control subset comprised 5% of preprocessed sequences randomly selected from the MSA and excluded from the training. The training control subset was built from a training dataset. Finally, the ancestral subset was composed of 100 reconstructed sequences by the straight evolutionary strategy. All controls contained the number of sequences corresponding to 5% of the preprocessed dataset.