Is MOGS p.Ala19fs (c.54dup) pathogenic?

MOGS p.Ala19fs (c.54dup) is classified Pathogenic in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-29). Very rare (popmax 8.69e-05%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Ala19fs (c.54dup)?

MOGS p.Ala19fs (c.54dup) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Ala19fs (c.54dup) in the general population?

MOGS p.Ala19fs (c.54dup) is very rare (popmax 8.69e-05%, nfe) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Ala19fs

c.54dup · rs1341709717 · VCV2913879

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.69e-05%, nfe)

Conditions

MOGS-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 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.57	GERP 0.25
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.69e-05% European (non-Finnish) · 1/1,150,684 alleles

Overall 6.51e-05% 1/1,535,020 alleles · very rare exomes 0/1,382,784 · genomes 1/152,236 · 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: MOGS
Protein: p.Ala19fs
Coding: c.54dup
MANE Select: NM_006302
dbSNP: rs1341709717
Type: Duplication
Location: chr2:74465193 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42
Residue 19: the 'disordered' region

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

Disease context

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

For MOGS-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MOGS p.Ala19= Conflicting classifications of pathogenicity ★ same residue
MOGS p.Glu418fs Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Leu664fs Uncertain significance ★★ same condition
MOGS p.Ala360fs Pathogenic ★ same condition
MOGS p.Asp152fs Likely pathogenic ★ same condition
MOGS p.Leu383fs Pathogenic ★ same condition
MOGS p.Ala621_Glu622insTer Conflicting classifications of pathogenicity ★ same condition
MOGS p.Pro747fs 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/mogs-p-ala19fs (accessed [today's date]).

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