Is ALG9 p.Ser393Arg (c.1177A>C) pathogenic?

ALG9 p.Ser393Arg (c.1177A>C) is classified Uncertain significance in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Absent from gnomAD v4.1; Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Ser393Arg (c.1177A>C)?

ALG9 p.Ser393Arg (c.1177A>C) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Ser393Arg (c.1177A>C) in the general population?

ALG9 p.Ser393Arg (c.1177A>C) 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.Ser393Arg

c.1177A>C · rs1555119958 · VCV1959895

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.
REVEL	0.015	strongly benign-leaning
Splicing
SpliceAI	Δ0.34	acceptor loss · deltas
Pangolin	Δ0.29	gain · loss 0.02 · SpliceAI calls loss · independent
Constraint at this position
Conservation	phyloP -3.8	GERP -3.6
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.028 · regional, not allelic
Overall
CADD	5.145	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.Ser393Arg
Coding: c.1177A>C
MANE Select: NM_024740
dbSNP: rs1555119958
Type: single nucleotide variant
Location: chr11:111838396 (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-ser393arg (accessed [today's date]).

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