Is CRPPA p.Pro5fs (c.6_13dup) pathogenic?

CRPPA p.Pro5fs (c.613dup) is classified Pathogenic in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). Very rare (popmax 0.0001%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2U.

What condition is associated with CRPPA p.Pro5fs (c.6_13dup)?

CRPPA p.Pro5fs (c.6_13dup) is associated with autosomal recessive limb-girdle muscular dystrophy type 2U, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (ClinVar).

How common is CRPPA p.Pro5fs (c.6_13dup) in the general population?

CRPPA p.Pro5fs (c.6_13dup) is very rare (popmax 0.0001%, nfe) (gnomAD).

How is ISPD-related limb-girdle muscular dystrophy R20 inherited?

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

CRPPA p.Pro5fs

c.6_13dup · rs2546759308 · VCV2941204

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0001%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2U

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 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP 0.22
Region caveats
Repeat context	tandem	(CCCGG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0001% European (non-Finnish) · 1/998,794 alleles

Overall 9.02e-05% 1/1,108,818 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CRPPA
Protein: p.Pro5fs
Coding: c.6_13dup
MANE Select: NM_001101426
dbSNP: rs2546759308
Type: Duplication
Location: chr7:16421309 (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 5: the 'disordered' region

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

Disease context

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

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

For ISPD-related limb-girdle muscular dystrophy R20 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CRPPA p.Pro5Ser Uncertain significance ★★ ⚠ same residue
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.Leu366fs Pathogenic ★ same condition
CRPPA p.Lys380Ter Pathogenic ★ same condition
CRPPA c.534+13dup Benign ★ 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-pro5fs (accessed [today's date]).

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