Is ALG2 p.Asp148fs (c.442_443del) pathogenic?

ALG2 p.Asp148fs (c.442443del) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Very rare (popmax 0.00223%, eas); Associated with ALG2-congenital disorder of glycosylation.

What condition is associated with ALG2 p.Asp148fs (c.442_443del)?

ALG2 p.Asp148fs (c.442_443del) is associated with ALG2-congenital disorder of glycosylation, congenital myasthenic syndrome 14 (ClinVar).

How common is ALG2 p.Asp148fs (c.442_443del) in the general population?

ALG2 p.Asp148fs (c.442_443del) is very rare (popmax 0.00223%, eas) (gnomAD).

How is ALG2-CDG inherited?

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

ALG2 p.Asp148fs

c.442_443del · rs1828743411 · VCV1471587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, 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	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.61	phastCons 0.89

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 6.84e-05% 1/1,461,820 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.Asp148fs
Coding: c.442_443del
MANE Select: NM_033087
dbSNP: rs1828743411
Type: Microsatellite
Location: chr9:99218742 (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

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.Asp148Gly Uncertain significance ★★ ⚠ same residue
ALG2 p.Ala87dup Uncertain significance ★ same condition
ALG2 p.Arg130del 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
ALG2 p.Ala29Pro Uncertain significance ★★ ⚠ same condition
ALG2 p.Ala36Val 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-asp148fs (accessed [today's date]).

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