Is MOGS p.Pro294Ala (c.880C>G) pathogenic?

MOGS p.Pro294Ala (c.880C>G) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-16). AlphaMissense: likely benign (0.0524); Ultra-rare (popmax 0.0468%, eas); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Pro294Ala (c.880C>G)?

MOGS p.Pro294Ala (c.880C>G) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Pro294Ala (c.880C>G) in the general population?

MOGS p.Pro294Ala (c.880C>G) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

What do computational predictors say about MOGS p.Pro294Ala (c.880C>G)?

AlphaMissense predicts likely benign (score 0.0524) — an in-silico prediction, not a clinical call.

MOGS p.Pro294Ala

c.880C>G · rs548283434 · VCV1368849

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0524 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0524	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.94, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,758 bp · p 0.9 · regional, not allelic
Overall
CADD	12.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0468% East Asian · 21/44,898 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0262%

Overall 0.00173% 28/1,614,036 alleles · ultra-rare exomes 27/1,461,796 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0468%	2,138
South Asian	0.0022%	45,544
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000339%	295,010

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.Pro294Ala
Coding: c.880C>G
MANE Select: NM_006302
dbSNP: rs548283434
Type: single nucleotide variant
Location: chr2:74462909 (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.Pro294Leu Benign/Likely benign ★★ same residue
MOGS p.Pro294Ser Uncertain significance ★ ⚠ same residue
MOGS p.Pro294fs Pathogenic ★ 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-pro294ala (accessed [today's date]).

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