Is ALG8 c.174+2del pathogenic?

ALG8 c.174+2del is classified Likely pathogenic in ALG8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-27). Absent from gnomAD; Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 c.174+2del?

ALG8 c.174+2del is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How common is ALG8 c.174+2del in the general population?

ALG8 c.174+2del 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 c.174+2del

rs2497144761 · VCV2118558

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

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	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	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
Coding: c.174+2del
MANE Select: NM_024079
dbSNP: rs2497144761
Type: Deletion
Location: chr11:78127356 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07

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

For ALG8-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG8 p.Arg268fs Pathogenic/Likely pathogenic ★★ same condition
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 p.Thr367fs Pathogenic ★ same condition
ALG8 p.Trp378fs Likely pathogenic ★ same condition
ALG8 c.95+8_95+23del Uncertain significance ★ 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-c-174-plus-2del (accessed [today's date]).

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