Is CRPPA p.Ser19fs (c.54_55delinsTGC) pathogenic?

CRPPA p.Ser19fs (c.5455delinsTGC) is classified Pathogenic in CRPPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-16). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2U.

What condition is associated with CRPPA p.Ser19fs (c.54_55delinsTGC)?

CRPPA p.Ser19fs (c.54_55delinsTGC) is associated with autosomal recessive limb-girdle muscular dystrophy type 2U (ClinVar).

How common is CRPPA p.Ser19fs (c.54_55delinsTGC) in the general population?

CRPPA p.Ser19fs (c.54_55delinsTGC) is absent from gnomAD (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.Ser19fs

c.54_55delinsTGC · rs2128321525 · VCV1342054

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -0.054	GERP -1.7

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRPPA
Protein: p.Ser19fs
Coding: c.54_55delinsTGC
MANE Select: NM_001101426
dbSNP: rs2128321525
Type: Indel
Location: chr7:16421268 (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 19: 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

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

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

CRPPA p.Ser19Glufs Pathogenic/Likely pathogenic ★★ same residue
CRPPA p.Ser19Arg Benign ★★ same residue
CRPPA c.789+89_789+90delinsGA Uncertain significance ★ same condition
CRPPA p.Glu292Arg Uncertain significance ★ same condition
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

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-ser19fs (accessed [today's date]).

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