Is MOGS p.Leu728Ser (c.2183T>C) pathogenic?

MOGS p.Leu728Ser (c.2183T>C) is classified Uncertain significance in MOGS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). AlphaMissense: likely pathogenic (0.9806); Absent from gnomAD v4.1.

How common is MOGS p.Leu728Ser (c.2183T>C) in the general population?

MOGS p.Leu728Ser (c.2183T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MOGS p.Leu728Ser (c.2183T>C)?

AlphaMissense predicts likely pathogenic (score 0.9806) — an in-silico prediction, not a clinical call.

MOGS p.Leu728Ser

c.2183T>C · VCV4681932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9806 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9806	likely pathogenic · top 1% in MOGS
REVEL	0.677	pathogenic-leaning
SaProt	LLR -16.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 601 bp · p 0.59 · regional, not allelic
Overall
CADD	27.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MOGS
Protein: p.Leu728Ser
Coding: c.2183T>C
MANE Select: NM_006302
Type: single nucleotide variant
Location: chr2:74461606 (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

Similar variants

MOGS p.Arg495Ter Pathogenic/Likely pathogenic ★★ same type
MOGS p.Gln124Ter Pathogenic ★★ same type
MOGS p.Gln505Ter Pathogenic/Likely pathogenic ★★ same type
MOGS p.Ala22Glu Uncertain significance ★★ ⚠ same type
MOGS p.Ala292Asp Uncertain significance ★★ ⚠ same type
MOGS p.Ala292Pro Uncertain significance ★★ ⚠ same type
MOGS p.Ala41Val Uncertain significance ★★ ⚠ same type
MOGS p.Ala510Thr Uncertain significance ★★ ⚠ same type

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-leu728ser (accessed [today's date]).

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