Is CRPPA p.Cys56fs (c.165dup) pathogenic?

CRPPA p.Cys56fs (c.165dup) is classified Pathogenic/Likely pathogenic in CRPPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-02-16). Very rare (popmax 0.0043%, sas); Associated with muscular dystrophy-dystroglycanopathy.

What condition is associated with CRPPA p.Cys56fs (c.165dup)?

CRPPA p.Cys56fs (c.165dup) is associated with muscular dystrophy-dystroglycanopathy (ClinVar).

How common is CRPPA p.Cys56fs (c.165dup) in the general population?

CRPPA p.Cys56fs (c.165dup) is very rare (popmax 0.0043%, sas) (gnomAD).

CRPPA p.Cys56fs

c.165dup · rs1554371369 · VCV435529

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0043%, sas)

Conditions

muscular dystrophy-dystroglycanopathy

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 0.71, phastCons 0.61

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0043% South Asian · 2/46,560 alleles

Filtering AF 0.000712% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000266%

Overall 0.000424% 5/1,179,224 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0043%	23,280
East Asian	0.00311%	32,204
European (non-Finnish)	0.000193%	517,625

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.Cys56fs
Coding: c.165dup
MANE Select: NM_001101426
dbSNP: rs1554371369
Type: Duplication
Location: chr7:16421157 (GRCh38)
Gene constraint: LOEUF 1.462 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.63 · 1 PDB

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

Disease context

muscular dystrophy-dystroglycanopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRPPA p.Ile93del Conflicting classifications of pathogenicity ★ same condition
CRPPA p.Ser19Glufs Pathogenic/Likely pathogenic ★★ same type
CRPPA c.836-19_836-18dup Benign/Likely benign ★★ same type
CRPPA c.836-19dup Benign ★★ same type
CRPPA p.Ala9fs Pathogenic ★ same type
CRPPA p.Gln352fs Likely pathogenic ★ same type
CRPPA p.Leu366fs Pathogenic ★ same type
CRPPA p.Lys380Ter Pathogenic ★ same type

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-cys56fs (accessed [today's date]).

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