Is ALG8 p.Asn290Ser (c.869A>G) pathogenic?

ALG8 p.Asn290Ser (c.869A>G) is classified Conflicting classifications of pathogenicity in ALG8 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-04-13). AlphaMissense: likely benign (0.0456); Rare (popmax 0.161%, afr); Associated with ALG8-congenital disorder of glycosylation.

What condition is associated with ALG8 p.Asn290Ser (c.869A>G)?

ALG8 p.Asn290Ser (c.869A>G) is associated with ALG8-congenital disorder of glycosylation, polycystic liver disease 3 with or without kidney cysts (ClinVar).

How common is ALG8 p.Asn290Ser (c.869A>G) in the general population?

ALG8 p.Asn290Ser (c.869A>G) is rare (popmax 0.161%, afr) (gnomAD).

How is ALG8-CDG inherited?

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

What do computational predictors say about ALG8 p.Asn290Ser (c.869A>G)?

AlphaMissense predicts likely benign (score 0.0456) — an in-silico prediction, not a clinical call.

ALG8 p.Asn290Ser

c.869A>G · rs61995923 · VCV701919

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0456 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.161%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ALG8-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0456	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.07, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 39 kb · p 0.14 · regional, not allelic
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.161% African / African-American · 121/75,052 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00892% 144/1,614,042 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.161%	620
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Admixed American	0.00333%	30,006
South Asian	0.0011%	91,078
European (non-Finnish)	0.000763%	131,104

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.Asn290Ser
Coding: c.869A>G
MANE Select: NM_024079
dbSNP: rs61995923
Type: single nucleotide variant
Location: chr11:78112679 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.07
Residue 290: 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 c.368+2T>G Likely pathogenic ★★ same condition
ALG8 c.674-2A>G Likely pathogenic ★★ same condition
ALG8 c.777+1G>A Likely pathogenic ★★ same condition
ALG8 c.95+1G>A Likely pathogenic ★★ same condition
ALG8 p.Arg179Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg268Ter Pathogenic/Likely pathogenic ★★ same condition
ALG8 p.Arg364Ter Pathogenic/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-asn290ser (accessed [today's date]).

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