Is ALG2 p.Glu30fs (c.89_114del) pathogenic?

ALG2 p.Glu30fs (c.89114del) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-02). Very rare (popmax 0.0033%, sas); Associated with congenital myasthenic syndrome 14.

What condition is associated with ALG2 p.Glu30fs (c.89_114del)?

ALG2 p.Glu30fs (c.89_114del) is associated with congenital myasthenic syndrome 14, ALG2-congenital disorder of glycosylation (ClinVar).

How common is ALG2 p.Glu30fs (c.89_114del) in the general population?

ALG2 p.Glu30fs (c.89_114del) is very rare (popmax 0.0033%, sas) (gnomAD).

How is ALG2-CDG inherited?

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

ALG2 p.Glu30fs

c.89_114del · rs775204090 · VCV1035954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

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 7.5	phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,036 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000813% 13/1,598,294 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,345
African / African-American	0.00267%	37,452
East Asian	0.00223%	44,864
European (non-Finnish)	0.000593%	168,498

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.Glu30fs
Coding: c.89_114del
MANE Select: NM_033087
dbSNP: rs775204090
Type: Deletion
Location: chr9:99221781 (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.Gly347fs Pathogenic/Likely pathogenic ★★ same condition
ALG2 p.Ala119_Cys120insTer Likely pathogenic ★ same condition
ALG2 p.Asp10_Ser11delinsAla Uncertain significance ★ same condition
ALG2 p.Cys45fs 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
ALG2 p.Ser11fs 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-glu30fs (accessed [today's date]).

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