Is ALG9 p.Thr43fs (c.126del) pathogenic?

ALG9 p.Thr43fs (c.126del) is classified Pathogenic in ALG9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). Very rare (popmax 0.00197%, amr); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Thr43fs (c.126del)?

ALG9 p.Thr43fs (c.126del) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Thr43fs (c.126del) in the general population?

ALG9 p.Thr43fs (c.126del) is very rare (popmax 0.00197%, amr) (gnomAD).

How is ALG9-CDG inherited?

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

ALG9 p.Thr43fs

c.126del · VCV3665027

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00197%, amr)

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.1	GERP -4.6
Region caveats
Repeat context	tandem	(CGCCG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00197% Admixed American · 1/50,746 alleles

Overall 6.54e-05% 1/1,529,630 alleles · very rare exomes 1/1,377,618 · genomes 0/152,012 · joint denominator

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: ALG9
Protein: p.Thr43fs
Coding: c.126del
MANE Select: NM_024740
Type: Deletion
Location: chr11:111871357 (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.1605_1608del Likely pathogenic ★ same condition
ALG9 p.Leu235fs Likely pathogenic ★ same condition
ALG9 p.Met331fs Pathogenic ★ same condition
ALG9 c.132-13del Benign ★ same condition
ALG9 c.1602+14del Likely benign ★ same condition
ALG9 c.1734-17del Benign ★ same condition
ALG9 c.702-9_702-8del Likely benign ★ same condition
ALG9 c.566-1G>A 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/alg9-p-thr43fs (accessed [today's date]).

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