Is MOGS p.Ala292Pro (c.874G>C) pathogenic?

MOGS p.Ala292Pro (c.874G>C) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1574); Ultra-rare (popmax 0.0574%, afr); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Ala292Pro (c.874G>C)?

MOGS p.Ala292Pro (c.874G>C) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Ala292Pro (c.874G>C) in the general population?

MOGS p.Ala292Pro (c.874G>C) is ultra-rare (popmax 0.0574%, afr) (gnomAD).

What do computational predictors say about MOGS p.Ala292Pro (c.874G>C)?

AlphaMissense predicts likely benign (score 0.1574) — an in-silico prediction, not a clinical call.

MOGS p.Ala292Pro

c.874G>C · rs763544524 · VCV858358

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1574	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -11.24	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 0.62	GERP 0.18, phastCons 0.54
Regional constraint	o/e 0.99	unconstrained · MANE · 2,758 bp · p 0.9 · regional, not allelic
Overall
CADD	17.4	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 0.0574% African / African-American · 43/74,944 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.039%

Overall 0.00762% 123/1,613,944 alleles · ultra-rare exomes 90/1,461,690 · genomes 33/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,743
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Finnishnot grpmax-eligible	0.00939%	10,649
European (non-Finnish)	0.00517%	19,345
Admixed American	0.005%	20,000
East Asian	0.00223%	44,894
South Asian	0.0011%	91,086

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.Ala292Pro
Coding: c.874G>C
MANE Select: NM_006302
dbSNP: rs763544524
Type: single nucleotide variant
Location: chr2:74462915 (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.Ala292Asp Uncertain significance ★★ ⚠ same residue
MOGS p.Ala292Ser Uncertain significance ★ ⚠ same residue
MOGS p.Ala292= 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.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-ala292pro (accessed [today's date]).

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