Is MOGS p.Pro350fs (c.1049del) pathogenic?

MOGS p.Pro350fs (c.1049del) is classified Likely pathogenic in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Very rare (popmax 0.00102%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Pro350fs (c.1049del)?

MOGS p.Pro350fs (c.1049del) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Pro350fs (c.1049del) in the general population?

MOGS p.Pro350fs (c.1049del) is very rare (popmax 0.00102%, nfe) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Pro350fs

c.1049del · VCV3586938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, 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	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.75	GERP -0.91, phastCons 0.11

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,038 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,240 alleles · very rare exomes 12/1,461,888 · genomes 0/152,352 · 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.Pro350fs
Coding: c.1049del
MANE Select: NM_006302
Type: Deletion
Location: chr2:74462740 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42

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.Pro350Arg Uncertain significance ★★ ⚠ same residue
MOGS p.Glu295fs Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Val216fs Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Asp141fs Pathogenic ★ same condition
MOGS p.Asp212fs Pathogenic ★ same condition
MOGS p.Gln408fs Pathogenic ★ same condition
MOGS p.His151fs Pathogenic ★ same condition
MOGS p.Ile402fs 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/mogs-p-pro350fs (accessed [today's date]).

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