Is ALG6 p.Phe250fs (c.732_748dup) pathogenic?

ALG6 p.Phe250fs (c.732748dup) is classified Likely pathogenic in ALG6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-01-10). Absent from gnomAD; Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Phe250fs (c.732_748dup)?

ALG6 p.Phe250fs (c.732_748dup) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Phe250fs (c.732_748dup) in the general population?

ALG6 p.Phe250fs (c.732_748dup) is absent from gnomAD (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Phe250fs

c.732_748dup · rs1553155823 · VCV556039

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ALG6-congenital disorder of glycosylation 1C

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 9 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -3.9

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: ALG6
Protein: p.Phe250fs
Coding: c.732_748dup
MANE Select: NM_013339
dbSNP: rs1553155823
Type: Duplication
Location: chr1:63411972 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.08

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.Phe250= Likely benign ★ same residue
ALG6 c.257+2dup Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Asp267delinsGlyTer Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Gly222fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Ile399fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Thr76fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.988-8dup Benign/Likely benign ★★ same condition
ALG6 c.902+2dup Likely pathogenic ★ 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-phe250fs (accessed [today's date]).

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