Is PREPL p.Ala244fs (c.730del) pathogenic?

PREPL p.Ala244fs (c.730del) is classified Likely pathogenic in PREPL (ClinVar, Single submitter, 1 submitter). Associated with myasthenic syndrome, congenital, 22.

What condition is associated with PREPL p.Ala244fs (c.730del)?

PREPL p.Ala244fs (c.730del) is associated with myasthenic syndrome, congenital, 22 (ClinVar).

How is Congenital myasthenic syndrome inherited?

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

PREPL p.Ala244fs

c.730del · VCV3383158

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

myasthenic syndrome, congenital, 22

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 7 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.3	GERP 2.5, phastCons 1

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

Variant & gene context

Gene: PREPL
Protein: p.Ala244fs
Coding: c.730del
MANE Select: NM_001171613
Type: Deletion
Location: chr2:44338509 (GRCh38)
Gene constraint: LOEUF 1.247 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 2 PDB

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

Disease context

myasthenic syndrome, congenital, 22 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital myasthenic syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

PREPL c.-42del Pathogenic/Likely pathogenic ★★ same condition
PREPL p.Leu56fs Pathogenic/Likely pathogenic ★★ same condition
PREPL p.Phe31fs Pathogenic/Likely pathogenic ★★ same condition
PREPL p.Phe339fs Pathogenic ★★ same condition
PREPL c.1412_1479+41del Likely pathogenic ★ same condition
PREPL c.-31_-28del Pathogenic ★ same condition
PREPL p.Asp124fs Pathogenic ★ same condition
PREPL p.Glu378fs 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/prepl-p-ala244fs (accessed [today's date]).

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