Is ALG9 p.Lys399= (c.1197A>G) pathogenic?

ALG9 p.Lys399= (c.1197A>G) is classified Uncertain significance in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-20). Absent from gnomAD v4.1; Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Lys399= (c.1197A>G)?

ALG9 p.Lys399= (c.1197A>G) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Lys399= (c.1197A>G) in the general population?

ALG9 p.Lys399= (c.1197A>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.

ALG9 p.Lys399=

c.1197A>G · rs2496967683 · VCV2008761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.33	acceptor gain, 23 bp away · masked 0 · deltas
Pangolin	Δ0.22	gain · loss 0.15 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2	GERP 0.59, phastCons 1
Overall
CADD	10.87	PHRED · no single calibrated threshold — expert panels disagree

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.Lys399=
Coding: c.1197A>G
MANE Select: NM_024740
dbSNP: rs2496967683
Type: single nucleotide variant
Location: chr11:111838376 (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 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
ALG9 c.*1722C>T 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-lys399 (accessed [today's date]).

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