Is MAGED2 p.Pro43Leu (c.128C>T) pathogenic?

MAGED2 p.Pro43Leu (c.128C>T) is classified Conflicting classifications of pathogenicity in MAGED2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0729); Ultra-rare (popmax 0.0618%, afr); Associated with Inborn genetic diseases.

What condition is associated with MAGED2 p.Pro43Leu (c.128C>T)?

MAGED2 p.Pro43Leu (c.128C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAGED2 p.Pro43Leu (c.128C>T) in the general population?

MAGED2 p.Pro43Leu (c.128C>T) is ultra-rare (popmax 0.0618%, afr) (gnomAD).

What do computational predictors say about MAGED2 p.Pro43Leu (c.128C>T)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

MAGED2 p.Pro43Leu

c.128C>T · rs201160051 · VCV3122179

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0618%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -7.28	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 0.065	GERP -2.5
Regional constraint	o/e 0.88	unconstrained · MANE · 1,781 bp · p 0.078 · regional, not allelic
Overall
CADD	4.914	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0618% African / African-American · 35/56,679 alleles

Filtering AF 0.0456% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00483% 58/1,201,746 alleles · ultra-rare exomes 31/1,090,945 · genomes 27/110,801 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0618%	1,619
Admixed American	0.0223%	4,485
Remaining individualsnot grpmax-eligible	0.00633%	15,793
East Asian	0.00299%	33,442
Finnishnot grpmax-eligible	0.00217%	46,027
European (non-Finnish)	0.000898%	111,379

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.Pro43Leu
Coding: c.128C>T
MANE Select: NM_177433
dbSNP: rs201160051
Type: single nucleotide variant
Location: chrX:54809804 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 43: 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-pro43leu (accessed [today's date]).

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