The chr6:138199775 T/TC substitution in the TNFAIP3 gene, classified as likely pathogenic, was identified in two SSc patients and associated with cutaneous, vascular, and joint manifestation, as well as ILD and esophagitis (χ2 = 16.3–40.9, p < 0.0001). The gene discussed is TNFAIP3; the disease is systemic sclerosis.