Deletion of a single nucleotide at c.138 (within codon 46, CTG→Leu) shifts the reading frame. The new frame encodes 8 aberrant amino acids (Phe-Gly-Val-Glu-Gly-Ser-Phe-Thr) before encountering a premature termination codon (TAG) at what would be residue position 54.

The resulting 53-residue peptide lacks all functional domains: no exonuclease activity, no polymerase activity, no C-terminal zinc-finger platform for holoenzyme assembly. The transcript is predicted to be degraded by nonsense-mediated mRNA decay (NMD), as the PTC is >50 nt upstream of the final exon–exon junction.

In the heterozygous state, the remaining wild-type allele must support all leading-strand synthesis. Complete loss of both alleles would be lethal given Pol ε’s essential role in S-phase DNA replication.