Is MOGS p.Arg678Trp (c.2032C>T) pathogenic?

MOGS p.Arg678Trp (c.2032C>T) is classified Benign/Likely benign in MOGS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-29). AlphaMissense: likely benign (0.0765); Common (popmax 8.15%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Arg678Trp (c.2032C>T)?

MOGS p.Arg678Trp (c.2032C>T) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

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.Arg678Trp (c.2032C>T)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

MOGS p.Arg678Trp

Q: How common is MOGS p.Arg678Trp (c.2032C>T) in the general population?

MOGS p.Arg678Trp (c.2032C>T) is common (popmax 8.15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2032C>T · rs13405869 · VCV337105

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.15%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP -0.7, phastCons 0.93
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	20.2	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 8.15% African / African-American · 6,115/75,028 alleles

Filtering AF 7.98% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.91%

Overall 0.437% 7,050/1,614,170 alleles · common exomes 3,523/1,461,876 · genomes 3,527/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.15%	12
Admixed American	0.523%	191
Remaining individualsnot grpmax-eligible	0.494%	202
Middle Eastern	0.247%	404
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
European (non-Finnish)	0.0224%	4,470
South Asian	0.0187%	5,358
Finnishnot grpmax-eligible	0.00156%	64,028

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.Arg678Trp
Coding: c.2032C>T
MANE Select: NM_006302
dbSNP: rs13405869
Type: single nucleotide variant
Location: chr2:74461757 (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.Arg678Gln Uncertain significance ★ ⚠ same residue
MOGS p.Arg678Leu 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

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-arg678trp (accessed [today's date]).

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