Is ALG2 p.Arg130del (c.385CGG[1]) pathogenic?

ALG2 p.Arg130del (c.385CGG[1]) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-17). Very rare (popmax 0.00186%, nfe); Associated with congenital myasthenic syndrome 14.

What condition is associated with ALG2 p.Arg130del (c.385CGG[1])?

ALG2 p.Arg130del (c.385CGG[1]) is associated with congenital myasthenic syndrome 14, ALG2-congenital disorder of glycosylation (ClinVar).

How common is ALG2 p.Arg130del (c.385CGG[1]) in the general population?

ALG2 p.Arg130del (c.385CGG[1]) is very rare (popmax 0.00186%, nfe) (gnomAD).

How is ALG2-CDG inherited?

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

ALG2 p.Arg130del

c.385CGG[1] · rs779134943 · VCV2069581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

congenital myasthenic syndrome 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,180,006 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00151% 22/1,457,656 alleles · very rare

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: ALG2
Protein: p.Arg130del
Coding: c.385CGG[1]
MANE Select: NM_033087
dbSNP: rs779134943
Type: Microsatellite
Location: chr9:99218795 (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.Arg130Gln Uncertain significance ★★ ⚠ same residue
ALG2 p.Arg130Trp Uncertain significance ★ ⚠ same residue
ALG2 p.Arg130= Benign ★ same residue
ALG2 p.Ala87dup Uncertain significance ★ same condition
ALG2 p.Asp148fs Uncertain significance ★ same condition
ALG2 p.Gly85dup Uncertain significance ★ same condition
ALG2 p.Gly347fs Pathogenic/Likely pathogenic ★★ same condition
ALG2 p.Gly72_Leu75delinsSerProArg Pathogenic/Likely 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/alg2-p-arg130del (accessed [today's date]).

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