〔Abstract〕 Objective To investigate the pathogenicity of rare damaging variants from ciliary pathway to human lumbosacral neural tube defects(NTDs). Methods The coding region sequences of 49 ciliary genes were amplified by AmpliSeq technique and sequenced by PGM sequencing platform for screening the rare damaging variants, and the parents without phenotype were used as controls to evaluate the pathogenicity of variants. Results The rare de novo mutation of GLI3 gene(c.C580 T,p.H194 Y) was detected in one patient.The rare complex heterozygous mutations of CRB2 gene(c.G1392 C,p.R464 S;c.T3448 C,p.C1150 R) was detected in another patient. Conclusion Rare damaging variants from ciliary pathway may be associated with the occurrence of human lumbosacral NTDs.