Is ALG2 p.Ser11fs (c.30del) pathogenic?

ALG2 p.Ser11fs (c.30del) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). Ultra-rare (popmax 0.0134%, eas); Associated with ALG2-congenital disorder of glycosylation.

What condition is associated with ALG2 p.Ser11fs (c.30del)?

ALG2 p.Ser11fs (c.30del) is associated with ALG2-congenital disorder of glycosylation, congenital myasthenic syndrome 14 (ClinVar).

How common is ALG2 p.Ser11fs (c.30del) in the general population?

ALG2 p.Ser11fs (c.30del) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is ALG2-CDG inherited?

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

ALG2 p.Ser11fs

c.30del · rs763575022 · VCV1016801

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

ALG2-congenital disorder of glycosylation

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 -1.4
Overall
CADD	15.54	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 0.0134% East Asian · 6/44,682 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00395%

Overall 0.000566% 9/1,591,408 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,447
Remaining individualsnot grpmax-eligible	0.00485%	20,633

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.Ser11fs
Coding: c.30del
MANE Select: NM_033087
dbSNP: rs763575022
Type: Deletion
Location: chr9:99221865 (GRCh38)
Gene constraint: LOEUF 1.408 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.03
Residue 11: a UniProt-annotated variant site (in)

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

Disease context

ALG2-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 14

For ALG2-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG2 p.Ser11Pro Benign ★★ same residue
ALG2 p.Ser11Leu Uncertain significance ★ ⚠ same residue
ALG2 p.Ser11= 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.Cys45fs Uncertain significance ★ same condition
ALG2 p.Glu30fs 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-ser11fs (accessed [today's date]).

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