Is CRPPA p.Cys198= (c.594C>T) pathogenic?

CRPPA p.Cys198= (c.594C>T) is classified Likely benign in CRPPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-01). Very rare (popmax 0.00835%, amr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2U.

What condition is associated with CRPPA p.Cys198= (c.594C>T)?

CRPPA p.Cys198= (c.594C>T) 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.Cys198= (c.594C>T) in the general population?

CRPPA p.Cys198= (c.594C>T) is very rare (popmax 0.00835%, amr) (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.Cys198=

c.594C>T · rs756333932 · VCV1146400

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00835%, amr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 3.7, phastCons 0.41
Overall
CADD	7.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00835% Admixed American · 5/59,904 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000616% 9/1,461,080 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00835%	11,981
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.000254%	393,201

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.Cys198=
Coding: c.594C>T
MANE Select: NM_001101426
dbSNP: rs756333932
Type: single nucleotide variant
Location: chr7:16376182 (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

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 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
CRPPA c.1119+3A>G 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-cys198 (accessed [today's date]).

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