Is MOGS p.Thr248Ile (c.743C>T) pathogenic?

MOGS p.Thr248Ile (c.743C>T) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1406); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with MOGS p.Thr248Ile (c.743C>T)?

MOGS p.Thr248Ile (c.743C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MOGS p.Thr248Ile (c.743C>T) in the general population?

MOGS p.Thr248Ile (c.743C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MOGS p.Thr248Ile (c.743C>T)?

AlphaMissense predicts likely benign (score 0.1406) — an in-silico prediction, not a clinical call.

MOGS p.Thr248Ile

c.743C>T · VCV4625158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1406 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1406	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -8.91	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 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,758 bp · p 0.9 · regional, not allelic
Overall
CADD	25.3	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 0.00223% East Asian · 1/44,904 alleles

Overall 6.2e-05% 1/1,614,048 alleles · very rare exomes 0/1,461,878 · genomes 1/152,170 · joint denominator

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.Thr248Ile
Coding: c.743C>T
MANE Select: NM_006302
Type: single nucleotide variant
Location: chr2:74463223 (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

Similar variants

MOGS p.Thr248Ala Uncertain significance ★ ⚠ same residue
MOGS p.Ala292Asp Uncertain significance ★★ ⚠ same condition
MOGS p.Ala292Pro Uncertain significance ★★ ⚠ same condition
MOGS p.Ala41Val Uncertain significance ★★ ⚠ same condition
MOGS p.Ala688Thr Uncertain significance ★★ ⚠ same condition
MOGS p.Ala780Thr Uncertain significance ★★ ⚠ same condition
MOGS p.Arg241His Uncertain significance ★★ ⚠ same condition
MOGS p.Arg280Pro 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-thr248ile (accessed [today's date]).

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