Is MOGS p.Asp718Glu (c.2154C>A) pathogenic?

MOGS p.Asp718Glu (c.2154C>A) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.2792); Absent from gnomAD v4.1; Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Asp718Glu (c.2154C>A)?

MOGS p.Asp718Glu (c.2154C>A) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Asp718Glu (c.2154C>A) in the general population?

MOGS p.Asp718Glu (c.2154C>A) 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.Asp718Glu (c.2154C>A)?

AlphaMissense predicts likely benign (score 0.2792) — an in-silico prediction, not a clinical call.

MOGS p.Asp718Glu

c.2154C>A · rs1671907085 · VCV1039485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.2792	likely benign
REVEL	0.487	indeterminate
SaProt	LLR -12.62	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -1.9, phastCons 0.83
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	19.93	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.Asp718Glu
Coding: c.2154C>A
MANE Select: NM_006302
dbSNP: rs1671907085
Type: single nucleotide variant
Location: chr2:74461635 (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.Asp718Asn Uncertain significance ★★ ⚠ same residue
MOGS p.Asp718= 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

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-asp718glu (accessed [today's date]).

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