Is MAGED2 p.Ala497Val (c.1490C>T) pathogenic?

MAGED2 p.Ala497Val (c.1490C>T) is classified Uncertain significance in MAGED2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: ambiguous (0.38); Absent from gnomAD v4.1.

How common is MAGED2 p.Ala497Val (c.1490C>T) in the general population?

MAGED2 p.Ala497Val (c.1490C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAGED2 p.Ala497Val (c.1490C>T)?

AlphaMissense predicts ambiguous (score 0.38) — an in-silico prediction, not a clinical call.

MAGED2 p.Ala497Val

c.1490C>T · rs2519311052 · VCV2025001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.38 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.38	ambiguous
REVEL	0.11	moderately benign-leaning
SaProt	LLR -9.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,336 bp · p 1.7e-14 · regional, not allelic
Overall
CADD	22.5	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

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.Ala497Val
Coding: c.1490C>T
MANE Select: NM_177433
dbSNP: rs2519311052
Type: single nucleotide variant
Location: chrX:54815351 (GRCh38)
Structure: AlphaFold pLDDT 59.89

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-ala497val (accessed [today's date]).

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