Is MAGED2 p.Ser5Arg (c.15C>G) pathogenic?

MAGED2 p.Ser5Arg (c.15C>G) is classified Uncertain significance in MAGED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0816); Very rare (popmax 0.000223%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAGED2 p.Ser5Arg (c.15C>G)?

MAGED2 p.Ser5Arg (c.15C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MAGED2 p.Ser5Arg (c.15C>G) in the general population?

MAGED2 p.Ser5Arg (c.15C>G) is very rare (popmax 0.000223%, nfe) (gnomAD).

What do computational predictors say about MAGED2 p.Ser5Arg (c.15C>G)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

MAGED2 p.Ser5Arg

c.15C>G · VCV4624175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.26	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 -10	GERP -3.6
Regional constraint	o/e 0.88	unconstrained · MANE · 1,781 bp · p 0.078 · regional, not allelic
Overall
CADD	9.041	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 0.000223% European (non-Finnish) · 2/895,063 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000165% 2/1,211,183 alleles · very rare exomes 2/1,097,720 · genomes 0/113,463 · 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: MAGED2
Protein: p.Ser5Arg
Coding: c.15C>G
MANE Select: NM_177433
Type: single nucleotide variant
Location: chrX:54809346 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 5: a modified residue (phosphoserine); the 'disordered' region

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.Ala389Gly Uncertain significance ★★ ⚠ same condition
MAGED2 p.Ala97Gly Uncertain significance ★★ ⚠ same condition
MAGED2 p.Pro436Ser 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-ser5arg (accessed [today's date]).

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