Is MOGS p.Gln684Pro (c.2051A>C) pathogenic?

MOGS p.Gln684Pro (c.2051A>C) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-23). AlphaMissense: ambiguous (0.3889); Absent from gnomAD v4.1; Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Gln684Pro (c.2051A>C)?

MOGS p.Gln684Pro (c.2051A>C) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Gln684Pro (c.2051A>C) in the general population?

MOGS p.Gln684Pro (c.2051A>C) is absent from gnomAD v4.1 (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.Gln684Pro (c.2051A>C)?

AlphaMissense predicts ambiguous (score 0.3889) — an in-silico prediction, not a clinical call.

MOGS p.Gln684Pro

c.2051A>C · rs2103976932 · VCV2071337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3889 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.3889	ambiguous
REVEL	0.36	indeterminate
SaProt	LLR -12.56	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	23.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MOGS
Protein: p.Gln684Pro
Coding: c.2051A>C
MANE Select: NM_006302
dbSNP: rs2103976932
Type: single nucleotide variant
Location: chr2:74461738 (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.Gln684= Likely benign ★ 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-gln684pro (accessed [today's date]).

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