Is ALG1 p.Val107fs (c.318dup) pathogenic?

ALG1 p.Val107fs (c.318dup) is classified Pathogenic in ALG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Very rare (popmax 8.47e-05%, nfe); Associated with ALG1-congenital disorder of glycosylation.

What condition is associated with ALG1 p.Val107fs (c.318dup)?

ALG1 p.Val107fs (c.318dup) is associated with ALG1-congenital disorder of glycosylation (ClinVar).

How common is ALG1 p.Val107fs (c.318dup) in the general population?

ALG1 p.Val107fs (c.318dup) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is ALG1-CDG inherited?

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

ALG1 p.Val107fs

c.318dup · rs2505849083 · VCV2855024

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

ALG1-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 3 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -0.39, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 6.84e-05% 1/1,461,888 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: ALG1
Protein: p.Val107fs
Coding: c.318dup
MANE Select: NM_019109
dbSNP: rs2505849083
Type: Duplication
Location: chr16:5073181 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG1 p.Leu15_Pro16insAlaLeuCysLeuLeuLeu Uncertain significance ★★ same condition
ALG1 p.Asn171fs Pathogenic ★ same condition
ALG1 p.Gln102fs Pathogenic ★ same condition
ALG1 p.Ile163fs Pathogenic ★ same condition
ALG1 p.Leu56fs Pathogenic ★ same condition
ALG1 p.Cys12_Leu17dup Conflicting classifications of pathogenicity ★ same condition
ALG1 p.Gln339dup Uncertain significance ★ same condition
ALG1 p.Ser258_Arg263dup 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/alg1-p-val107fs (accessed [today's date]).

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