Objective:Fibrodysplasia ossificans progressiva(FOP) is a rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification(HO),associated with the mutation in the activin A type 1 receptor / activin-like kinase 2(ACVR1/ALK2) gene. The purpose of this study was to report one FOP patient with atypical clinical findings and to identify the genetic entity. Methods: Clinical diagnosis was based on physical examination,radiological findings and biochemical tests. For mutation detection,the blood samples from the FOP patient,his parents and 60 normal controls were collected with informed consent. Genomic DNA was isolated from peripheral lymphocytes and all the exons of ACVR1 were amplified by PCR. The PCR products sequenced directly with the cycle sequencing methods. Then we generated the three-dimensional model of protein structure for the cytoplasmic domain of the R258S in ACVR1 to evaluate its receptor function. Results: The patient had congenital minimal malformations of the great toes and radiographic evidence of heterotopic ossification at the time of evaluation. The process of heterotopic bone formation was a mild course and did not follow the typical temporal and spatial patterns. Analysis of ACVR1 gene revealed that the patient had a heterozygous missense mutation,c.774 G>C(R258S),which is located in the kinase domain of ACVR1. We also find that all the people,including the patient,the parents and 60 normal controls,occurred nonsense mutation,c.690 G> A(E230E). In the protein modeling,ARG258 and SER194 can form the H-bonds. When the ARG258 is substituted by SER,the H-bonds are lost,so the αGS1 and the αC helix conformations do shift and make ACVR1 into an“open” conformation and constituently activated. Conclusion: Most patients showing typical FOP phenotypes have the heterozygous c.617G>A(R206H) mutation belonging to the GS domain of ACVR1. Our report describes a patient affected with FOP showing mild progressive symptoms,and these atypical FOP phenotypes may associate with a novel mutation(c.774 G>C),affecting a conserved residue of the ACVR1 kinase domain.Our findings make the relations between phenotypes and genotypes of FOP better understood.