Is ALG2 p.Cys45fs (c.132del) pathogenic?

ALG2 p.Cys45fs (c.132del) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). Absent from gnomAD; Associated with congenital myasthenic syndrome 14.

What condition is associated with ALG2 p.Cys45fs (c.132del)?

ALG2 p.Cys45fs (c.132del) is associated with congenital myasthenic syndrome 14, ALG2-congenital disorder of glycosylation (ClinVar).

How common is ALG2 p.Cys45fs (c.132del) in the general population?

ALG2 p.Cys45fs (c.132del) is absent from gnomAD (gnomAD).

How is ALG2-CDG inherited?

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

ALG2 p.Cys45fs

c.132del · rs2490392043 · VCV1999036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital myasthenic syndrome 14

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 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	phastCons 1

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: ALG2
Protein: p.Cys45fs
Coding: c.132del
MANE Select: NM_033087
dbSNP: rs2490392043
Type: Deletion
Location: chr9:99221763 (GRCh38)
Gene constraint: LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.03

Full ALG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG2-congenital disorder of glycosylation

For ALG2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG2 p.Cys45= Likely benign ★ same residue
ALG2 p.Gly347fs Pathogenic/Likely pathogenic ★★ same condition
ALG2 p.Ala119_Cys120insTer Likely pathogenic ★ same condition
ALG2 p.Asp10_Ser11delinsAla Uncertain significance ★ same condition
ALG2 p.Glu30fs Uncertain significance ★ same condition
ALG2 p.Lys308fs Uncertain significance ★ same condition
ALG2 p.Met386fs Uncertain significance ★ same condition
ALG2 p.Phe103fs 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/alg2-p-cys45fs (accessed [today's date]).

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