FKRP p.Asp74fs
c.221_234delinsGAA · VCV4816130
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
autosomal recessive limb-girdle muscular dystrophy type 2I
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 9.1 | GERP 1.4, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- FKRP
- Protein
- p.Asp74fs
- Coding
- c.221_234delinsGAA
- MANE Select
- NM_024301
- Type
- Indel
- Location
- chr19:46755671 (GRCh38)
- Gene constraint
- LOEUF 1.543 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.08 · 8 PDB
Disease context
autosomal recessive limb-girdle muscular dystrophy type 2I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor FKRP-related limb-girdle muscular dystrophy R9 (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult, Childhood
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- FKRP p.Ala336fs Likely pathogenic ★ same condition
- FKRP p.Pro186fs Likely pathogenic ★ same condition
- FKRP p.Arg167_Cys168delinsSerArg Conflicting classifications of pathogenicity ★ same condition
- FKRP p.Pro90fs Likely pathogenic same condition
- FKRP p.Ala397fs Pathogenic ★★ same condition
- FKRP p.Ala455Asp Pathogenic ★★ same condition
- FKRP p.Arg176Ter Pathogenic/Likely pathogenic ★★ same condition
- FKRP p.Arg229fs Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/fkrp-p-asp74fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown