Is ALG8 p.Arg268fs (c.802del) pathogenic?

ALG8 p.Arg268fs (c.802del) is classified Pathogenic/Likely pathogenic in ALG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-09). Absent from gnomAD; Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Arg268fs (c.802del)?

ALG8 p.Arg268fs (c.802del) is associated with ALG8-congenital disorder of glycosylation, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Arg268fs (c.802del) in the general population?

ALG8 p.Arg268fs (c.802del) is absent from gnomAD (gnomAD).

How is ALG8-CDG inherited?

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

ALG8 p.Arg268fs

c.802del · rs2136899636 · VCV1437904

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 8 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 2.2, phastCons 1

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: ALG8
Protein: p.Arg268fs
Coding: c.802del
MANE Select: NM_024079
dbSNP: rs2136899636
Type: Deletion
Location: chr11:78112746 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 268: 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: polycystic liver disease 3 with or without kidney cysts

For ALG8-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same residue
ALG8 p.Arg268Gln Benign/Likely benign ★★ ⚠ same residue
ALG8 p.Arg268Leu Uncertain significance ★ ⚠ same residue
ALG8 p.Asn91fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Gly275fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Trp353fs Likely pathogenic ★★ same condition
ALG8 c.174+30del Benign ★★ same condition
ALG8 c.174+2del 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-arg268fs (accessed [today's date]).

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