Is ALG9 p.Ile359Met (c.1077A>G) pathogenic?

ALG9 p.Ile359Met (c.1077A>G) is classified Uncertain significance in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-12). AlphaMissense: likely benign (0.0639); Absent from gnomAD v4.1; Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Ile359Met (c.1077A>G)?

ALG9 p.Ile359Met (c.1077A>G) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Ile359Met (c.1077A>G) in the general population?

ALG9 p.Ile359Met (c.1077A>G) is absent from gnomAD v4.1 (gnomAD).

How is ALG9-CDG inherited?

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

What do computational predictors say about ALG9 p.Ile359Met (c.1077A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

ALG9 p.Ile359Met

c.1077A>G · rs2497028867 · VCV2110229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.1	GERP -3.7, phastCons 0.002
Regional constraint	o/e 0.40	unconstrained · MANE · 3,925 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	0.864	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALG9
Protein: p.Ile359Met
Coding: c.1077A>G
MANE Select: NM_024740
dbSNP: rs2497028867
Type: single nucleotide variant
Location: chr11:111840751 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB

Full ALG9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG9-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG9-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG9 p.Ile359Val Uncertain significance ★ ⚠ same residue
ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG9 c.896-2A>G Likely pathogenic ★★ same condition
ALG9 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Trp248Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Tyr287Cys Pathogenic/Likely pathogenic ★★ same condition
ALG9 c.*1607C>T Uncertain significance ★★ same condition
ALG9 c.*1624A>C 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/alg9-p-ile359met (accessed [today's date]).

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