Is MOGS p.Tyr685= (c.2055T>C) pathogenic?

MOGS p.Tyr685= (c.2055T>C) is classified Conflicting classifications of pathogenicity in MOGS (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-06-01). Rare (popmax 0.197%, nfe); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Tyr685= (c.2055T>C)?

MOGS p.Tyr685= (c.2055T>C) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Tyr685= (c.2055T>C) in the general population?

MOGS p.Tyr685= (c.2055T>C) is rare (popmax 0.197%, nfe) (gnomAD).

How is MOGS-CDG inherited?

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

MOGS p.Tyr685=

c.2055T>C · rs202094225 · VCV281500

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.197%, 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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.16	GERP 0.7, phastCons 0.085
Overall
CADD	1.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.197% European (non-Finnish) · 2,326/1,180,032 alleles

Filtering AF 0.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.158% 2,557/1,614,188 alleles · rare exomes 2,369/1,461,890 · genomes 188/152,298 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.197%	507
Remaining individualsnot grpmax-eligible	0.173%	579
Admixed American	0.152%	660
African / African-American	0.0373%	2,680
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Finnishnot grpmax-eligible	0.00156%	64,040

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.Tyr685=
Coding: c.2055T>C
MANE Select: NM_006302
dbSNP: rs202094225
Type: single nucleotide variant
Location: chr2:74461734 (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.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-tyr685 (accessed [today's date]).

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