What condition is associated with FKRP p.Pro186fs (c.557_573delinsTGGGGGAGACGCAGCCCAGGGG)?

FKRP p.Pro186fs (c.557_573delinsTGGGGGAGACGCAGCCCAGGGG) is associated with autosomal recessive limb-girdle muscular dystrophy type 2I (ClinVar).

How is FKRP-related limb-girdle muscular dystrophy R9 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FKRP p.Pro186fs

Q: Is FKRP p.Pro186fs (c.557_573delinsTGGGGGAGACGCAGCCCAGGGG) pathogenic?

FKRP p.Pro186fs (c.557573delinsTGGGGGAGACGCAGCCCAGGGG) is classified Likely pathogenic in FKRP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). Associated with autosomal recessive limb-girdle muscular dystrophy type 2I.

c.557_573delinsTGGGGGAGACGCAGCCCAGGGG · VCV4816132

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

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 2	GERP 1.1, phastCons 0.006

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: FKRP
Protein: p.Pro186fs
Coding: c.557_573delinsTGGGGGAGACGCAGCCCAGGGG
MANE Select: NM_024301
Type: Indel
Location: chr19:46756007 (GRCh38)
Gene constraint: LOEUF 1.543 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.08 · 8 PDB
Residue 186: a turn

Full FKRP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2I — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 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.Pro186Leu Uncertain significance ★★ ⚠ same residue
FKRP p.Pro186= Likely benign ★★ same residue
FKRP p.Ala336fs Likely pathogenic ★ same condition
FKRP p.Asp74fs Likely pathogenic ★ same condition
FKRP p.Arg167_Cys168delinsSerArg Conflicting classifications of pathogenicity ★ same condition
FKRP p.Pro186Ala Uncertain significance ★ ⚠ same residue
FKRP p.Pro90fs Likely pathogenic same condition
FKRP p.Ala397fs 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-pro186fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown