Is CRPPA p.Glu239fs (c.716_719del) pathogenic?

CRPPA p.Glu239fs (c.716719del) is classified Pathogenic in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-16). Very rare (popmax 0.00554%, sas); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7.

How common is CRPPA p.Glu239fs (c.716_719del) in the general population?

CRPPA p.Glu239fs (c.716_719del) is very rare (popmax 0.00554%, sas) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

CRPPA p.Glu239fs

Q: What condition is associated with CRPPA p.Glu239fs (c.716_719del)?

CRPPA p.Glu239fs (c.716_719del) 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.716_719del · VCV3759109

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00554%, sas)

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 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.92	GERP -3.3, phastCons 0.99

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00554% South Asian · 5/90,214 alleles

Filtering AF 0.00212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.000411% 6/1,458,492 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00554%	18,043
Admixed American	0.00167%	59,792

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.Glu239fs
Coding: c.716_719del
MANE Select: NM_001101426
Type: Deletion
Location: chr7:16308593 (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 239: a UniProt-annotated variant site (in mddgc7; atypical form presenting with congenital muscular dystrophy)

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.Glu239Lys Uncertain significance ★★ ⚠ same residue
CRPPA p.Val62fs Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.836-9del Benign/Likely benign ★★ same condition
CRPPA c.(278+1_279-1 Likely pathogenic ★ same condition
CRPPA c.534+1del Pathogenic ★ same condition
CRPPA c.769_789+179del Likely pathogenic ★ same condition
CRPPA p.Asn390_Leu391insTer Pathogenic ★ same condition
CRPPA p.Glu235fs 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-glu239fs (accessed [today's date]).

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