DYSF p.Pro147=

The NM_003494.4: c.438T>C p.(Pro146=) variant in DYSF, which is also known as NM_001130987.2: c.441T>C p.(Pro147=), is a synonymous variant that does not affect the protein amino acid sequence. It is not located in a splice region and is not predicted to affect splicing (SpliceAI score 0) (BP4, BP7). This variant has been reported in an individual with disease range dysferlin expression in blood monocytes (Jain Foundation Dysferlin Registry internal data communication), but it was identified in a heterozygous state with two other DYSF variants: one classified as pathogenic by the VCEP and the other a splice region variant predicted to ablate a canonical donor site that has been observed in multiple patients. However, phase was not determined (BP2 not met). This variant fails quality filters in gnomAD v4.1.0 exomes but is absent from genomes (PM2_Supporting). In summary, this variant meets criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy. Although there are both pathogenic and benign types of evidence for this variant, the population frequency is not considered inconsistent with the final classification. ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 2.0.0; 04/30/2026): BP4, BP7, PM2_Supporting.