Is ALG6 p.Ser340fs (c.1018del) pathogenic?

ALG6 p.Ser340fs (c.1018del) is classified Pathogenic/Likely pathogenic in ALG6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-24). Very rare (popmax 0.00051%, nfe); Associated with ALG6-congenital disorder of glycosylation 1C.

What condition is associated with ALG6 p.Ser340fs (c.1018del)?

ALG6 p.Ser340fs (c.1018del) is associated with ALG6-congenital disorder of glycosylation 1C (ClinVar).

How common is ALG6 p.Ser340fs (c.1018del) in the general population?

ALG6 p.Ser340fs (c.1018del) is very rare (popmax 0.00051%, nfe) (gnomAD).

How is ALG6-CDG inherited?

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

ALG6 p.Ser340fs

c.1018del · rs1269984067 · VCV965480

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00051%, 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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.58	GERP -2, phastCons 0.93
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00051% European (non-Finnish) · 6/1,176,152 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000374% 6/1,605,408 alleles · very rare

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.Ser340fs
Coding: c.1018del
MANE Select: NM_013339
dbSNP: rs1269984067
Type: Deletion
Location: chr1:63419397 (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 c.82_82+8del Likely pathogenic ★★ same condition
ALG6 p.Asn283fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Gln417fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Leu416fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Met34fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Phe228fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Phe336fs Pathogenic/Likely pathogenic ★★ same condition
ALG6 p.Pro379fs 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-ser340fs (accessed [today's date]).

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