Is ALG2 p.Arg251Cys (c.750_751delinsTT) pathogenic?

ALG2 p.Arg251Cys (c.750751delinsTT) is classified Uncertain significance in ALG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). No gnomAD frequency available for this variant; Associated with ALG2-congenital disorder of glycosylation.

What condition is associated with ALG2 p.Arg251Cys (c.750_751delinsTT)?

ALG2 p.Arg251Cys (c.750_751delinsTT) is associated with ALG2-congenital disorder of glycosylation, congenital myasthenic syndrome 14 (ClinVar).

How common is ALG2 p.Arg251Cys (c.750_751delinsTT) in the general population?

ALG2 p.Arg251Cys (c.750_751delinsTT) is no gnomAD frequency available for this variant (gnomAD).

How is ALG2-CDG inherited?

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

ALG2 p.Arg251Cys

c.750_751delinsTT · rs2490383282 · VCV2116214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ALG2-congenital disorder of glycosylation

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 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 3,957 bp · p 0.038 · regional, not allelic

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.Arg251Cys
Coding: c.750_751delinsTT
MANE Select: NM_033087
dbSNP: rs2490383282
Type: Indel
Location: chr9:99218434 (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.Arg251His Uncertain significance ★★ ⚠ same residue
ALG2 p.Arg251Leu Pathogenic ⚠ same residue
ALG2 p.Gly72_Leu75delinsSerProArg Pathogenic/Likely pathogenic ★★ same condition
ALG2 p.Asp73fs Likely pathogenic ★ same condition
ALG2 p.Ser352fs Conflicting classifications of pathogenicity ★ 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-arg251cys (accessed [today's date]).

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