Is MOGS p.Leu664fs (c.1988dup) pathogenic?

MOGS p.Leu664fs (c.1988dup) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-21). Very rare (popmax 0.000678%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Leu664fs (c.1988dup)?

MOGS p.Leu664fs (c.1988dup) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Leu664fs (c.1988dup) in the general population?

MOGS p.Leu664fs (c.1988dup) is very rare (popmax 0.000678%, nfe) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Leu664fs

c.1988dup · rs1558564895 · VCV1392069

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, 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 -0.021	GERP -0.69, phastCons 0.64

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,030 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000681% 11/1,614,206 alleles · very rare exomes 11/1,461,878 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)grpmax	0.000678%	147,504

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu664fs
Coding: c.1988dup
MANE Select: NM_006302
dbSNP: rs1558564895
Type: Duplication
Location: chr2:74461800 (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.Glu418fs Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Ala19fs Pathogenic ★ 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
MOGS p.Tyr560Ter 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-leu664fs (accessed [today's date]).

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