Human cytomegalovirus (HCMV) viral chemokine, UL146, and TNF alpha-like receptor UL144 genes show a high degree of hypervariability in clinical isolates. These proteins are predicted to be immune modulators and may contribute to the pathogenesis of HCMV infections. We analyzed the UL146 and UL144 genetic variation of 51 HCMV isolates from congenitally infected children and 13 isolates from children in childcare. There was no statistically significant correlation between UL146 and UL144 genotypes and HCMV disease and/or sequelae. However, there were some groups that had a relatively large proportion of asymptomatic outcomes. These included UL146 group 8 (7/8 asymptomatic) and UL146 group 10 (3/3 asymptomatic). UL144 group B had 11/15 (73%) asymptomatic. UL146 and UL144 genes remained stable in serial isolates from children in daycare for intervals up to three years. These results indicate that most UL146 and UL144 genotypes do not predict clinical sequelae following congenital HCMV infections.