Clusterin (CLU) and clathrin assembly lymphoid myeloid (CALM) protein are implicated in the function of neuronal synapses. However, to our knowledge, whether they play roles in the maldevelopment of synaptic pathways in schizophrenia has not been studied. The purpose of this study was to examine whether single nucleotide polymorphisms rs11136000 within the CLU gene and rs3851179 within the CALM gene, were associated with schizophrenia. Polymorphisms rs11136000 and rs3851179 were analyzed among 184 Chinese patients with schizophrenia and 162 healthy controls. The high-resolution melting method was used to genotype the two loci. Patients with schizophrenia and with family history showed a significant increase of allele C frequency in rs11136000 in comparison to normal controls (p = 0.03). In addition, the C allele frequency was also higher in patients with negative symptoms (p = 0.04). In contrast, allele and genotype frequencies of rs3851179 did not show significant differences between patients and normal subjects or between patients with different symptoms. The results of this study show that polymorphism of the CLU gene may confer symptomatic specificity in schizophrenia, whereas polymorphism of the CALM gene does not affect susceptibility to schizophrenia.