Is MOGS p.Arg486Thr (c.1457G>C) pathogenic?

MOGS p.Arg486Thr (c.1457G>C) is classified Pathogenic in MOGS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-06-01). AlphaMissense: likely pathogenic (0.9732); Absent from gnomAD v4.1; Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Arg486Thr (c.1457G>C)?

MOGS p.Arg486Thr (c.1457G>C) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg486Thr (c.1457G>C) in the general population?

MOGS p.Arg486Thr (c.1457G>C) is absent from gnomAD v4.1 (gnomAD).

How is MOGS-CDG inherited?

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

What do computational predictors say about MOGS p.Arg486Thr (c.1457G>C)?

AlphaMissense predicts likely pathogenic (score 0.9732) — an in-silico prediction, not a clinical call.

MOGS p.Arg486Thr

c.1457G>C · rs121909291 · VCV8193

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9732 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.9732	likely pathogenic ✓ concordant with ClinVar · top 2% in MOGS
REVEL	0.703	pathogenic-leaning
SaProt	LLR -15.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 608 bp · p 6e-07 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MOGS
Protein: p.Arg486Thr
Coding: c.1457G>C
MANE Select: NM_006302
dbSNP: rs121909291
Type: single nucleotide variant
Location: chr2:74462332 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.42
Residue 486: a UniProt-annotated variant site (in cdgiib; loss of activity)

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-arg486thr (accessed [today's date]).

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