Is MAGED2 p.Pro113Leu (c.338C>T) pathogenic?

MAGED2 p.Pro113Leu (c.338C>T) is classified Likely benign in MAGED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-04). AlphaMissense: likely benign (0.0562); Ultra-rare (popmax 0.0133%, amr).

How common is MAGED2 p.Pro113Leu (c.338C>T) in the general population?

MAGED2 p.Pro113Leu (c.338C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about MAGED2 p.Pro113Leu (c.338C>T)?

AlphaMissense predicts likely benign (score 0.0562) — an in-silico prediction, not a clinical call.

MAGED2 p.Pro113Leu

c.338C>T · rs763271575 · VCV1972064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0562 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0562	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.61	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 -0.063	GERP -2.8
Regional constraint	o/e 0.88	unconstrained · MANE · 1,781 bp · p 0.078 · regional, not allelic
Overall
CADD	8.993	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 0.0133% Admixed American · 6/45,268 alleles

Filtering AF 0.00575% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00391%

Overall 0.00191% 23/1,204,166 alleles · ultra-rare exomes 22/1,093,502 · genomes 1/110,664 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,545
South Asian	0.00896%	11,164
European (non-Finnish)	0.00134%	74,357

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.Pro113Leu
Coding: c.338C>T
MANE Select: NM_177433
dbSNP: rs763271575
Type: single nucleotide variant
Location: chrX:54810014 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 113: the 'disordered' region

Full MAGED2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAGED2 p.Pro113fs Likely pathogenic ★ same residue
MAGED2 p.Ala389Gly Uncertain significance ★★ ⚠ same type
MAGED2 p.Ala97Gly Uncertain significance ★★ ⚠ same type
MAGED2 p.Arg257His Uncertain significance ★★ ⚠ same type
MAGED2 p.Pro153Ser Uncertain significance ★★ ⚠ same type
MAGED2 p.Pro436Ser Uncertain significance ★★ ⚠ same type
MAGED2 c.1085+101A>G Benign ★★ same type
MAGED2 c.1166-46C>A Benign ★★ 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/maged2-p-pro113leu (accessed [today's date]).

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