Introduction: Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia-1 (EDM1) are two rare skeletal diseases with substantial clinical overlap, caused by variants in the gene coding cartilage oligomeric matrix protein (COMP). Objectives: To summarize the clinical characteristics of PSACH/EDM1 and variants of COMP gene, as well as to explore the correlations between them. Methods: PubMed, China National Knowledge Infrastructure, and Wanfang were searched for case reports and case series of patients with genetic diagnosis of PSACH/EDM1 from the inception to 24 March 2025. Results: A total of 830 PSACH/EDM1 patients (471probands) harboring 224 different variants of COMP gene were enrolled from 106 articles, with missense variants accounting for the majority (80.8%). Exon 13 (183 probands, 38.9%) and type III (T3) repeat domain (413 probands, 87.7%) were the most commonly affected regions, with c.1417_1419del (p.Asp473del) being the most common hotspot variant. Compared with EDM1, PSACH manifested earlier age of onset, shorter stature, higher rates of lower limb deformity, joint laxity, anterior beaking of the vertebra and irregular/flared metaphysis, while lower rate of joint pain/osteoarthritis and abnormal femoral head. Missense variants in T3-4 and T3-5 were more likely to cause EDM1, while those in T3-1 and T3-6 to T3-8 were associated with a greater frequency of PSACH. Majority of in-frame variants were found in PSACH, as c.1417_1419del being PSACH specific. Conclusions: PSACH exhibits more severe phenotypes than EDM1. Missense variants in T3-1 and T3-6 to T3-8, and in-frame variants are more strongly associated with PSACH, as the hotspot variant c.1417_1419del exclusively identified in PSACH