Is MOGS p.Arg468Trp (c.1402C>T) pathogenic?

MOGS p.Arg468Trp (c.1402C>T) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-25). AlphaMissense: likely benign (0.2439); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Arg468Trp (c.1402C>T)?

MOGS p.Arg468Trp (c.1402C>T) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg468Trp (c.1402C>T) in the general population?

MOGS p.Arg468Trp (c.1402C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about MOGS p.Arg468Trp (c.1402C>T)?

AlphaMissense predicts likely benign (score 0.2439) — an in-silico prediction, not a clinical call.

MOGS p.Arg468Trp

c.1402C>T · rs930452465 · VCV1990765

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2439	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -13.63	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 1.6	GERP -0.76, phastCons 0.008
Regional constraint	o/e 0.69	unconstrained · MANE · 608 bp · p 6e-07 · regional, not allelic
Overall
CADD	23.6	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 0.00833% Admixed American · 5/60,014 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000558% 9/1,614,048 alleles · very rare exomes 7/1,461,750 · genomes 2/152,298 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,003
African / African-American	0.00133%	75,050
South Asian	0.0011%	91,082
European (non-Finnish)	0.000169%	589,995

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.Arg468Trp
Coding: c.1402C>T
MANE Select: NM_006302
dbSNP: rs930452465
Type: single nucleotide variant
Location: chr2:74462387 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: MOGS-congenital disorder of glycosylation

Similar variants

MOGS p.Arg468Gln Uncertain significance ★ ⚠ same residue
MOGS p.Arg468Gly 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-arg468trp (accessed [today's date]).

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