Is ALG6 p.Ile299del (c.894AAT[1]) pathogenic?

ALG6 p.Ile299del (c.894AAT[1]) is classified Pathogenic/Likely pathogenic in ALG6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-07-09). Very rare (popmax 0.00358%, nfe); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Ile299del (c.894AAT[1])?

ALG6 p.Ile299del (c.894AAT[1]) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Ile299del (c.894AAT[1]) in the general population?

ALG6 p.Ile299del (c.894AAT[1]) is very rare (popmax 0.00358%, nfe) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Ile299del

c.894AAT[1] · rs387906338 · VCV30420

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00358%, nfe)

Conditions

ALG6-congenital disorder of glycosylation 1C

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 -0.74	GERP -3.4
Overall
CADD	14.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00358% European (non-Finnish) · 42/1,173,262 alleles

Filtering AF 0.00268% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00238%

Overall 0.00268% 43/1,606,420 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00358%	27,935
Remaining individualsnot grpmax-eligible	0.00161%	62,224

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: ALG6
Protein: p.Ile299del
Coding: c.894AAT[1]
MANE Select: NM_013339
dbSNP: rs387906338
Type: Microsatellite
Location: chr1:63414137 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08
Residue 299: a UniProt-annotated variant site (in cdg1c)

Full ALG6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG6-congenital disorder of glycosylation 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG6-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG6 p.Phe264fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Val169fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Tyr85fs Pathogenic ★ same condition
ALG6 p.Arg262del Uncertain significance ★ same condition
ALG6 p.Glu415del Uncertain significance ★ same condition
ALG6 p.Val239del Uncertain significance ★ same condition
ALG6 c.681-4_681-3insGTTTTTTTGTTTGTTT Likely benign ★ same condition
ALG6 p.Ile493dup 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/alg6-p-ile299del (accessed [today's date]).

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