Too Common to Ignore: Decoding the Complexity of the FGG p.Ala108Gly Variant in Fibrinogen Disorders.

Abstract

Abstract: This commentary expands on the article "Congenital Fibrinogen Deficiencies: Not So Rare" in Hämostaseologie (PMID: 40074015) with a specific focus on the FGG p.Ala108Gly variant. Although genome-wide association studies suggest that this common variant reduces fibrinogen levels and is classified as "likely pathogenic," its clinical significance remains debated. We review current evidence from case reports highlighting that most individuals with heterozygous for p.Ala108Gly have normal fibrinogen levels, whereas hypofibrinogenemia is mainly observed in those with additional fibrinogen gene alterations. Nonetheless, some carriers with normal fibrinogen levels exhibit bleeding symptoms, indicating a genotype-phenotype discrepancy. In conclusion, our paper along with the existing literature illustrates the clinical complexity of the FGG p.Ala108Gly variant. Given its high prevalence, further case-based studies are needed to clarify the controversial aspects of this variant and to define its clinical relevance in congenital fibrinogen disorder.