A multifactorial aetiology with genetic and environmental factors is assumed for orofacial clefts. Submucous cleft palate (SMCP), a subgroup of cleft palates with insufficient median fusion of the muscles of the soft palate hidden under the mucosa, has a prevalence of 1:1,250-1:5,000. We described the prevalence of risk factors among 103 German patients with the subtype SMCP and genotyped 24 single nucleotide polymorphisms (SNPs) from 12 candidate genes for orofacial clefts. Analysis of risk factors yielded a positive history for maternal cigarette smoking during pregnancy in 25.2% of the patients, and this was significantly more frequent than in the normal population. The group of patients differed in allele frequencies at SNP rs3917192 of the gene TGFB3 (nominal P = 0.053) and at SNP rs5752638 of the gene MN1 (nominal P = 0.075) compared with 279 control individuals. Our results indicate a potential role of maternal smoking during pregnancy for the formation of SMCP. The analysis of genetic variants hints at the contribution of TGFB3 and MN1 in the aetiology of SMCPs.