Is MOGS p.Gly4= (c.12C>G) pathogenic?

MOGS p.Gly4= (c.12C>G) is classified Benign/Likely benign in MOGS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Rare (popmax 0.172%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Gly4= (c.12C>G)?

MOGS p.Gly4= (c.12C>G) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Gly4= (c.12C>G) in the general population?

MOGS p.Gly4= (c.12C>G) is rare (popmax 0.172%, nfe) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Gly4=

c.12C>G · rs555329045 · VCV384985

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, nfe)

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.68 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.6	GERP 1.3, phastCons 1
Overall
CADD	12.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% European (non-Finnish) · 1,912/1,113,940 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.139% 2,003/1,442,906 alleles · rare exomes 1,868/1,290,598 · genomes 135/152,308 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.172%	583
Remaining individualsnot grpmax-eligible	0.0686%	1,457
Admixed American	0.0566%	1,767
Finnishnot grpmax-eligible	0.0376%	2,662
Middle Eastern	0.024%	4,162
African / African-American	0.0208%	4,818
Ashkenazi Jewishnot grpmax-eligible	0.00934%	10,706
South Asian	0.00152%	65,902

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.Gly4=
Coding: c.12C>G
MANE Select: NM_006302
dbSNP: rs555329045
Type: single nucleotide variant
Location: chr2:74465236 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42
Residue 4: 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.Gly4Ala Uncertain significance ★ ⚠ same residue
MOGS p.Gly4Asp Uncertain significance ★ ⚠ same residue
MOGS p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Gln124Ter Pathogenic ★★ same condition
MOGS p.Gln505Ter Pathogenic/Likely pathogenic ★★ same condition
MOGS p.Ala22Glu Uncertain significance ★★ ⚠ same condition
MOGS p.Ala292Asp Uncertain significance ★★ ⚠ same condition
MOGS p.Ala292Pro 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-gly4 (accessed [today's date]).

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