Is MOGS p.Arg609Cys (c.1825C>T) pathogenic?

MOGS p.Arg609Cys (c.1825C>T) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-20). AlphaMissense: likely benign (0.2099); Ultra-rare (popmax 0.0164%, mid); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Arg609Cys (c.1825C>T)?

MOGS p.Arg609Cys (c.1825C>T) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg609Cys (c.1825C>T) in the general population?

MOGS p.Arg609Cys (c.1825C>T) is ultra-rare (popmax 0.0164%, mid) (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.Arg609Cys (c.1825C>T)?

AlphaMissense predicts likely benign (score 0.2099) — an in-silico prediction, not a clinical call.

MOGS p.Arg609Cys

c.1825C>T · rs369797433 · VCV465839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2099 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2099	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -13.82	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.42, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 608 bp · p 6e-07 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00217% 35/1,613,930 alleles · ultra-rare exomes 30/1,461,848 · genomes 5/152,082 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.005%	19,997
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00401%	24,958
European (non-Finnish)	0.00212%	47,201

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.Arg609Cys
Coding: c.1825C>T
MANE Select: NM_006302
dbSNP: rs369797433
Type: single nucleotide variant
Location: chr2:74461964 (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.Arg609His 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-arg609cys (accessed [today's date]).

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