Achondroplasia (ACH; OMIM# 100800) is a genetic disease, an autosomal dominant skeletal dysplasia with associated phenotype of disproponate short-limbed dwarfism. The only causative gene responsible for disorder is Fibroblast growth factor receptor 3 (FGFR3, OMIM# 134934), located on chromosome 4p16.3 with 19 exons. Along with this ,FGFR3 also described for certain other genetic abnormalities like lacrimoauriculo-dento-digital (LADD) syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, epidermal nevi , SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans), thanatophoric dysplasia, camptodactyly, tall stature, hearing loss syndrome (CATSHL syndrome). The current study designed for investigation of a Pakistani family with short stature disproponate skeletal dysplasia without cousin marriage history. Affected girl was 2.5years old born from short height parents indicated severe clinical and radiological phenotypes including severe short-limbed short stature with marked ossification abnormalities and significant delay in speech. Our affected members reported with very short upper and lower limbs with large head circumference which differentiated from other disorders. Genomic DNA was extracted from the proband and proceeded for whole-exome sequencing. A novel missense mutation (c.1144 G>A, p.Gly382Arg) in FGFR3 gene was identified and confirmed its cosegregation within family by Sanger sequencing which is predicted to cause damaging effects and likely to lead nonsense mediated abnormality. This confirm the fact that pathogenic variant in FGFR3 is the major cause of achondroplasia and may be for other related phenotypes. The novel missense variant in FGFR3 gene is responsible for the unique phenotype of skeletal dysplasia (achondroplasia)