Is MOGS p.Arg820Cys (c.2458C>T) pathogenic?

MOGS p.Arg820Cys (c.2458C>T) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.161); Very rare (popmax 0.00223%, eas); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Arg820Cys (c.2458C>T)?

MOGS p.Arg820Cys (c.2458C>T) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg820Cys (c.2458C>T) in the general population?

MOGS p.Arg820Cys (c.2458C>T) is very rare (popmax 0.00223%, eas) (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.Arg820Cys (c.2458C>T)?

AlphaMissense predicts likely benign (score 0.161) — an in-silico prediction, not a clinical call.

MOGS p.Arg820Cys

c.2458C>T · rs370469058 · VCV2419669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.161	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,896 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00143% 23/1,613,972 alleles · very rare exomes 22/1,461,720 · genomes 1/152,252 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asiangrpmax	0.00223%	44,896
European (non-Finnish)	0.00153%	65,558

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.Arg820Cys
Coding: c.2458C>T
MANE Select: NM_006302
dbSNP: rs370469058
Type: single nucleotide variant
Location: chr2:74461331 (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.Arg820His 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
MOGS p.Ala41Val 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-arg820cys (accessed [today's date]).

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