Is ALG2 p.Ser352fs (c.1055_1056delinsTGA) pathogenic?

ALG2 p.Ser352fs (c.10551056delinsTGA) is classified Conflicting classifications of pathogenicity in ALG2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with ALG2 p.Ser352fs (c.1055_1056delinsTGA)?

ALG2 p.Ser352fs (c.1055_1056delinsTGA) is associated with Inborn genetic diseases, ALG2-congenital disorder of glycosylation, congenital myasthenic syndrome 14 (ClinVar).

How common is ALG2 p.Ser352fs (c.1055_1056delinsTGA) in the general population?

ALG2 p.Ser352fs (c.1055_1056delinsTGA) is absent from gnomAD (gnomAD).

ALG2 p.Ser352fs

c.1055_1056delinsTGA · rs1554707637 · VCV464893

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Inborn genetic diseases

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 0.16	GERP -2.7, phastCons 0.001

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.Ser352fs
Coding: c.1055_1056delinsTGA
MANE Select: NM_033087
dbSNP: rs1554707637
Type: Indel
Location: chr9:99218129 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ALG2-congenital disorder of glycosylation congenital myasthenic syndrome 14

Similar variants

ALG2 p.Ser352delinsLeuThr Uncertain significance ★ same residue
ALG2 p.Ser352= Likely benign ★ same residue
ALG2 p.Gly72_Leu75delinsSerProArg Pathogenic/Likely pathogenic ★★ same condition
ALG2 p.Asp73fs Likely pathogenic ★ same condition
ALG2 p.Arg251Cys Uncertain significance ★ same condition
ALG2 p.Gly347fs 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-ser352fs (accessed [today's date]).

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