Is CRPPA p.Leu366fs (c.1097dup) pathogenic?

CRPPA p.Leu366fs (c.1097dup) is classified Pathogenic in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7.

How is Walker-Warburg syndrome inherited?

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

CRPPA p.Leu366fs

Q: What condition is associated with CRPPA p.Leu366fs (c.1097dup)?

CRPPA p.Leu366fs (c.1097dup) is associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, autosomal recessive limb-girdle muscular dystrophy type 2U (ClinVar).

c.1097dup · VCV4793536

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.8	GERP -2.3

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

Variant & gene context

Gene: CRPPA
Protein: p.Leu366fs
Coding: c.1097dup
MANE Select: NM_001101426
Type: Duplication
Location: chr7:16258411 (GRCh38)
Gene constraint: LOEUF 1.462 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.63 · 1 PDB
Residue 366: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy); an α-helix

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

Disease context

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2U

For Walker-Warburg syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (United Kingdom)

Similar variants

CRPPA p.Ser19Glufs Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.836-19_836-18dup Benign/Likely benign ★★ same condition
CRPPA c.836-19dup Benign ★★ same condition
CRPPA p.Ala9fs Pathogenic ★ same condition
CRPPA p.Lys380Ter Pathogenic ★ same condition
CRPPA p.Pro5fs Pathogenic ★ same condition
CRPPA c.534+13dup Benign ★ same condition
CRPPA c.1120-1G>T 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/crppa-p-leu366fs (accessed [today's date]).

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