Is MOGS p.Pro748His (c.2243C>A) pathogenic?

MOGS p.Pro748His (c.2243C>A) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-16). AlphaMissense: likely pathogenic (0.7643); Very rare (popmax 0.0022%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Pro748His (c.2243C>A)?

MOGS p.Pro748His (c.2243C>A) is associated with Inborn genetic diseases, MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Pro748His (c.2243C>A) in the general population?

MOGS p.Pro748His (c.2243C>A) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about MOGS p.Pro748His (c.2243C>A)?

AlphaMissense predicts likely pathogenic (score 0.7643) — an in-silico prediction, not a clinical call.

MOGS p.Pro748His

c.2243C>A · rs369937053 · VCV534241

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7643	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -15.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0022% European (non-Finnish) · 26/1,179,930 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00167% 27/1,614,032 alleles · very rare exomes 24/1,461,688 · genomes 3/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,382
African / African-American	0.00133%	75,042

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.Pro748His
Coding: c.2243C>A
MANE Select: NM_006302
dbSNP: rs369937053
Type: single nucleotide variant
Location: chr2:74461546 (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.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
MOGS p.Ala510Thr 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-pro748his (accessed [today's date]).

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