Is ALG8 p.Gly275fs (c.824del) pathogenic?

ALG8 p.Gly275fs (c.824del) is classified Pathogenic/Likely pathogenic in ALG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-21). Very rare (popmax 0.00668%, eas); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Gly275fs (c.824del)?

ALG8 p.Gly275fs (c.824del) is associated with ALG8-congenital disorder of glycosylation, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Gly275fs (c.824del) in the general population?

ALG8 p.Gly275fs (c.824del) is very rare (popmax 0.00668%, eas) (gnomAD).

How is ALG8-CDG inherited?

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

ALG8 p.Gly275fs

c.824del · rs745894763 · VCV2982294

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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 1.2	GERP 0.46, phastCons 1
Overall
CADD	34.0	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 0.00668% East Asian · 3/44,890 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,920 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.Gly275fs
Coding: c.824del
MANE Select: NM_024079
dbSNP: rs745894763
Type: Deletion
Location: chr11:78112724 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 275: a UniProt-annotated variant site (in pcld3); a UniProt-annotated variant site (in cdg1h; decreased dolichyl pyrophosphate glc1man9glcnac2 alpha-1,3-glucosyltransferase activity)

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.Gly275Asp Likely pathogenic ★ same residue
ALG8 p.Gly275Val Uncertain significance ★ ⚠ same residue
ALG8 p.Arg268fs Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Asn91fs 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
ALG8 p.Thr367fs 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-gly275fs (accessed [today's date]).

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