Is ALG8 p.Ser372fs (c.1114dup) pathogenic?

ALG8 p.Ser372fs (c.1114dup) is classified Likely pathogenic in ALG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-01). Very rare (popmax 8.47e-05%, nfe); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Ser372fs (c.1114dup)?

ALG8 p.Ser372fs (c.1114dup) is associated with ALG8-congenital disorder of glycosylation, familial cystic renal disease, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Ser372fs (c.1114dup) in the general population?

ALG8 p.Ser372fs (c.1114dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is ALG8-CDG inherited?

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

ALG8 p.Ser372fs

c.1114dup · VCV3574039

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

ALG8-congenital disorder of glycosylation

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 10 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 6.84e-05% 1/1,461,852 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: ALG8
Protein: p.Ser372fs
Coding: c.1114dup
MANE Select: NM_024079
Type: Duplication
Location: chr11:78106870 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 372: a UniProt-annotated variant site (in pcld3)

Full ALG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG8-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial cystic renal disease polycystic liver disease 3 with or without kidney cysts

For ALG8-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG8 p.Ser372= Likely benign ★ same residue
ALG8 p.Leu104fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Pro255fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Val328fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Glu452fs Pathogenic ★ same condition
ALG8 p.Ile46fs Likely pathogenic ★ same condition
ALG8 p.Leu241fs Likely pathogenic ★ same condition
ALG8 p.Trp55fs 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/alg8-p-ser372fs (accessed [today's date]).

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