Is CRPPA p.Pro384= (c.1152C>T) pathogenic?

CRPPA p.Pro384= (c.1152C>T) is classified Likely benign in CRPPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-30). Very rare (popmax 0.00449%, eas); Associated with muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7.

How common is CRPPA p.Pro384= (c.1152C>T) in the general population?

CRPPA p.Pro384= (c.1152C>T) is very rare (popmax 0.00449%, eas) (gnomAD).

How is Walker-Warburg syndrome inherited?

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

CRPPA p.Pro384=

Q: What condition is associated with CRPPA p.Pro384= (c.1152C>T)?

CRPPA p.Pro384= (c.1152C>T) 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.1152C>T · rs765231439 · VCV2931762

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00449%, eas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP -0.34
Overall
CADD	0.757	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% East Asian · 2/44,536 alleles

Filtering AF 0.000744% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000279%

Overall 0.000209% 3/1,434,274 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00449%	22,268
European (non-Finnish)	8.62e-05%	1,160,087

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.Pro384=
Coding: c.1152C>T
MANE Select: NM_001101426
dbSNP: rs765231439
Type: single nucleotide variant
Location: chr7:16216165 (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 384: 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.Pro384Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CRPPA c.1120-1G>T Pathogenic ★★ same condition
CRPPA c.258-1G>C Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.835+2T>C Pathogenic/Likely pathogenic ★★ same condition
CRPPA p.Arg184Ter Pathogenic ★★ same condition
CRPPA p.Arg268Ter Pathogenic ★★ same condition
CRPPA p.Gln215Ter Pathogenic/Likely pathogenic ★★ same condition
CRPPA c.1026+5G>C Uncertain significance ★★ 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-pro384 (accessed [today's date]).

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