Is MOGS p.Thr375Ile (c.1124C>T) pathogenic?

MOGS p.Thr375Ile (c.1124C>T) is classified Uncertain significance in MOGS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-31). AlphaMissense: likely benign (0.0947); Rare (popmax 0.297%, amr); Associated with MOGS-congenital disorder of glycosylation.

What condition is associated with MOGS p.Thr375Ile (c.1124C>T)?

MOGS p.Thr375Ile (c.1124C>T) is associated with MOGS-congenital disorder of glycosylation (ClinVar).

How common is MOGS p.Thr375Ile (c.1124C>T) in the general population?

MOGS p.Thr375Ile (c.1124C>T) is rare (popmax 0.297%, amr) (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.Thr375Ile (c.1124C>T)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

MOGS p.Thr375Ile

c.1124C>T · rs200888878 · VCV534243

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.297%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MOGS-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -9.88	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 5	GERP 0.29, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,758 bp · p 0.9 · regional, not allelic
Overall
CADD	17.44	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 0.297% Admixed American · 178/60,020 alleles

Filtering AF 0.261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.247%

Overall 0.012% 193/1,614,252 alleles · rare exomes 91/1,461,888 · genomes 102/152,364 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.297%	337
Remaining individualsnot grpmax-eligible	0.0128%	7,814
East Asian	0.0111%	8,976
African / African-American	0.00133%	75,070
South Asian	0.0011%	91,090

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.Thr375Ile
Coding: c.1124C>T
MANE Select: NM_006302
dbSNP: rs200888878
Type: single nucleotide variant
Location: chr2:74462665 (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.Thr375Asn Uncertain significance ★ ⚠ 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-thr375ile (accessed [today's date]).

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