Is MAGED2 p.Pro436Ser (c.1306C>T) pathogenic?

MAGED2 p.Pro436Ser (c.1306C>T) is classified Uncertain significance in MAGED2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-30). AlphaMissense: likely pathogenic (0.9936); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAGED2 p.Pro436Ser (c.1306C>T)?

MAGED2 p.Pro436Ser (c.1306C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAGED2 p.Pro436Ser (c.1306C>T) in the general population?

MAGED2 p.Pro436Ser (c.1306C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAGED2 p.Pro436Ser (c.1306C>T)?

AlphaMissense predicts likely pathogenic (score 0.9936) — an in-silico prediction, not a clinical call.

MAGED2 p.Pro436Ser

c.1306C>T · rs369099604 · VCV2087025

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9936 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9936	likely pathogenic · top 5% in MAGED2
REVEL	0.33	indeterminate
SaProt	LLR -12.88	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 7.3	GERP 2, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,336 bp · p 1.7e-14 · regional, not allelic
Overall
CADD	25.2	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: MAGED2
Protein: p.Pro436Ser
Coding: c.1306C>T
MANE Select: NM_177433
dbSNP: rs369099604
Type: single nucleotide variant
Location: chrX:54814695 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 436: the mage domain

Full MAGED2 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

MAGED2 p.Pro436= Likely benign ★ same residue
MAGED2 p.Ala389Gly Uncertain significance ★★ ⚠ same condition
MAGED2 p.Ala97Gly Uncertain significance ★★ ⚠ same condition
MAGED2 p.Thr296Met Benign/Likely benign ★★ same condition
MAGED2 c.991-6C>T Uncertain significance ★ same condition
MAGED2 p.Ala115Val Uncertain significance ★ ⚠ same condition
MAGED2 p.Ala150Glu Uncertain significance ★ ⚠ same condition
MAGED2 p.Ala235Thr 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/maged2-p-pro436ser (accessed [today's date]).

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