Is MOGS p.Pro294fs (c.881del) pathogenic?

MOGS p.Pro294fs (c.881del) is classified Pathogenic in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-21). Ultra-rare (popmax 0.011%, sas); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Pro294fs (c.881del)?

MOGS p.Pro294fs (c.881del) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Pro294fs (c.881del) in the general population?

MOGS p.Pro294fs (c.881del) is ultra-rare (popmax 0.011%, sas) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Pro294fs

c.881del · rs750486813 · VCV2846552

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

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 0.2	GERP 0.31, phastCons 0.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,082 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.000991% 16/1,613,982 alleles · ultra-rare exomes 16/1,461,662 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,108
East Asian	0.00223%	44,884
European (non-Finnish)	0.000424%	235,986

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.Pro294fs
Coding: c.881del
MANE Select: NM_006302
dbSNP: rs750486813
Type: Deletion
Location: chr2:74462908 (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.Pro294Ala Uncertain significance ★★ ⚠ same residue
MOGS p.Pro294Leu Benign/Likely benign ★★ 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

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-pro294fs (accessed [today's date]).

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