Is MAGED2 p.Arg476Ter (c.1426C>T) pathogenic?

MAGED2 p.Arg476Ter (c.1426C>T) is classified Likely pathogenic in MAGED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-22). Very rare (popmax 0.00266%, amr).

How common is MAGED2 p.Arg476Ter (c.1426C>T) in the general population?

MAGED2 p.Arg476Ter (c.1426C>T) is very rare (popmax 0.00266%, amr) (gnomAD).

MAGED2 p.Arg476Ter

c.1426C>T · rs1249585923 · VCV1712860

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00266%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 13
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 0.86, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% Admixed American · 1/37,568 alleles

Overall 8.58e-05% 1/1,165,781 alleles · very rare exomes 1/1,052,196 · genomes 0/113,585 · 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.Arg476Ter
Coding: c.1426C>T
MANE Select: NM_177433
dbSNP: rs1249585923
Type: single nucleotide variant
Location: chrX:54815287 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 476: the mage domain

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

Similar variants

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
MAGED2 c.1208+122G>C 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-arg476ter (accessed [today's date]).

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