Is ALG8 c.174+30del pathogenic?

ALG8 c.174+30del is classified Benign in ALG8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-14). Common (popmax 79.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 c.174+30del?

ALG8 c.174+30del is associated with ALG8-congenital disorder of glycosylation (ClinVar).

How is ALG8-CDG inherited?

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

ALG8 c.174+30del

Q: How common is ALG8 c.174+30del in the general population?

ALG8 c.174+30del is common (popmax 79.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs59662312 · VCV1188964

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 79.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +30	near-intronic (+30 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.2
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 79.3% African / African-American · 52,930/66,752 alleles

Filtering AF 78.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 78.5%

Overall 60.3% 798,709/1,324,078 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	79.3%	1
Finnishnot grpmax-eligible	64.2%	2
South Asian	62.2%	2
Middle Eastern	62.1%	2
East Asian	61.3%	2
Remaining individualsnot grpmax-eligible	61%	2
European (non-Finnish)	59%	2
Ashkenazi Jewishnot grpmax-eligible	57.7%	2
Amishnot grpmax-eligible	53.3%	2
Admixed American	52.2%	2

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
Coding: c.174+30del
MANE Select: NM_024079
dbSNP: rs59662312
Type: Deletion
Location: chr11:78127328 (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+2del Likely pathogenic ★ 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-30del (accessed [today's date]).

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