Is ALG3 p.Pro39fs (c.116del) pathogenic?

ALG3 p.Pro39fs (c.116del) is classified Pathogenic in ALG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). Very rare (popmax 8.49e-05%, nfe); Associated with ALG3-congenital disorder of glycosylation.

What condition is associated with ALG3 p.Pro39fs (c.116del)?

ALG3 p.Pro39fs (c.116del) is associated with ALG3-congenital disorder of glycosylation (ClinVar).

How common is ALG3 p.Pro39fs (c.116del) in the general population?

ALG3 p.Pro39fs (c.116del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

How is ALG3-CDG inherited?

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

ALG3 p.Pro39fs

c.116del · VCV3588985

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

ALG3-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 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.6	GERP -3, phastCons 0.024

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,662 alleles

Overall 6.87e-05% 1/1,456,566 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: ALG3
Protein: p.Pro39fs
Coding: c.116del
MANE Select: NM_005787
Type: Deletion
Location: chr3:184248825 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.05

Full ALG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG3-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG3-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG3 p.His297fs Pathogenic ★ same condition
ALG3 p.Lys72fs Likely pathogenic ★ same condition
ALG3 p.Pro39Leu Uncertain significance ★ ⚠ same residue
ALG3 c.196+19del Likely benign ★ same condition
ALG3 c.933-20_933-17del Likely benign ★ same condition
ALG3 c.163_196+3del Pathogenic same condition
ALG3 c.444+1G>T Likely pathogenic ★★ same condition
ALG3 p.Arg171Gln 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/alg3-p-pro39fs (accessed [today's date]).

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