Is ALG1 p.Asp289Gly (c.866A>G) pathogenic?

ALG1 p.Asp289Gly (c.866A>G) is classified Likely pathogenic in ALG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-06). AlphaMissense: likely pathogenic (0.9503); Very rare (popmax 0.0011%, nfe); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Asp289Gly (c.866A>G)?

ALG1 p.Asp289Gly (c.866A>G) is associated with ALG1-congenital disorder of glycosylation, congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Asp289Gly (c.866A>G) in the general population?

ALG1 p.Asp289Gly (c.866A>G) is very rare (popmax 0.0011%, nfe) (gnomAD).

How is ALG1-CDG inherited?

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

What do computational predictors say about ALG1 p.Asp289Gly (c.866A>G)?

AlphaMissense predicts likely pathogenic (score 0.9503) — an in-silico prediction, not a clinical call.

ALG1 p.Asp289Gly

c.866A>G · rs1180515976 · VCV690314

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9503 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG1-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9503	likely pathogenic ✓ concordant with ClinVar · top 10% in ALG1
REVEL	0.81	moderately pathogenic-leaning
SaProt	LLR -13.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.21	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.1	GERP 1.5, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	32.0	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 0.0011% European (non-Finnish) · 13/1,179,700 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000812% 13/1,600,180 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: ALG1
Protein: p.Asp289Gly
Coding: c.866A>G
MANE Select: NM_019109
dbSNP: rs1180515976
Type: single nucleotide variant
Location: chr16:5079067 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24
Residue 289: a UniProt-annotated variant site (in cdg1k; decreased function in protein glycosylation as shown by rescue assays in an alg1-deficient yeast strain)

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital disorder of glycosylation

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG1 p.Asp289= Likely benign ★★ same residue
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.1187+2T>C Pathogenic ★★ same condition
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.209-2A>G Likely pathogenic ★★ same condition
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG1 c.630-2A>G Likely pathogenic ★★ same condition
ALG1 c.863-2A>G 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/alg1-p-asp289gly (accessed [today's date]).

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