Is MOGS p.Arg674Gln (c.2021G>A) pathogenic?

MOGS p.Arg674Gln (c.2021G>A) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-14). AlphaMissense: ambiguous (0.3522); Rare (popmax 0.131%, afr); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Arg674Gln (c.2021G>A)?

MOGS p.Arg674Gln (c.2021G>A) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Arg674Gln (c.2021G>A) in the general population?

MOGS p.Arg674Gln (c.2021G>A) is rare (popmax 0.131%, afr) (gnomAD).

What do computational predictors say about MOGS p.Arg674Gln (c.2021G>A)?

AlphaMissense predicts ambiguous (score 0.3522) — an in-silico prediction, not a clinical call.

MOGS p.Arg674Gln

c.2021G>A · rs200966949 · VCV659690

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3522 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.131%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3522	ambiguous
REVEL	0.421	indeterminate
SaProt	LLR -13.66	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	25.5	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

Grpmax group 0.131% African / African-American · 98/75,050 alleles

Filtering AF 0.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00768% 124/1,614,212 alleles · rare exomes 67/1,461,882 · genomes 57/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.131%	766
Middle Eastern	0.0165%	6,062
Admixed American	0.015%	6,670
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.0011%	90,773

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.Arg674Gln
Coding: c.2021G>A
MANE Select: NM_006302
dbSNP: rs200966949
Type: single nucleotide variant
Location: chr2:74461768 (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.Arg674Trp Uncertain significance ★★ same residue
MOGS p.Arg674Leu Uncertain significance ★ ⚠ same residue
MOGS p.Arg674Pro 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

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-arg674gln (accessed [today's date]).

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