Is ALG6 p.Trp246fs (c.737_738delinsC) pathogenic?

ALG6 p.Trp246fs (c.737738delinsC) is classified Likely pathogenic in ALG6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-16). Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Trp246fs (c.737_738delinsC)?

ALG6 p.Trp246fs (c.737_738delinsC) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How is ALG6-CDG inherited?

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

ALG6 p.Trp246fs

c.737_738delinsC · VCV3587390

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 12	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: ALG6
Protein: p.Trp246fs
Coding: c.737_738delinsC
MANE Select: NM_013339
Type: Indel
Location: chr1:63411982 (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.Trp246Ter Likely pathogenic ★ same residue
ALG6 p.Leu334fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Ala77fs Likely pathogenic ★ same condition
ALG6 p.Phe398fs Likely pathogenic ★ same condition
ALG6 c.1128-1G>A Likely pathogenic ★★ same condition
ALG6 c.1128-2A>C Likely pathogenic ★★ same condition
ALG6 c.1326+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG6 c.257+2dup Pathogenic/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-trp246fs (accessed [today's date]).

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