Is MOGS p.Tyr99= (c.297C>T) pathogenic?

MOGS p.Tyr99= (c.297C>T) is classified Likely benign in MOGS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-08). Ultra-rare (popmax 0.0209%, amr); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Tyr99= (c.297C>T)?

MOGS p.Tyr99= (c.297C>T) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Tyr99= (c.297C>T) in the general population?

MOGS p.Tyr99= (c.297C>T) is ultra-rare (popmax 0.0209%, amr) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Tyr99=

c.297C>T · rs375679925 · VCV389407

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, amr)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.27, phastCons 1
Overall
CADD	8.315	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% Admixed American · 12/57,310 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00937%

Overall 0.0015% 24/1,595,040 alleles · ultra-rare exomes 22/1,442,764 · genomes 2/152,276 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0209%	4,776
Remaining individualsnot grpmax-eligible	0.00324%	30,829
European (non-Finnish)	0.000855%	117,014

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.Tyr99=
Coding: c.297C>T
MANE Select: NM_006302
dbSNP: rs375679925
Type: single nucleotide variant
Location: chr2:74464951 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42
Residue 99: the 'required for endoplasmic reticulum targeting' 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.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
MOGS p.Ala41Val Uncertain significance ★★ ⚠ same condition
MOGS p.Ala510Thr 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-tyr99 (accessed [today's date]).

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