Is MAGED2 p.Ala577Thr (c.1729G>A) pathogenic?

MAGED2 p.Ala577Thr (c.1729G>A) is classified Benign in MAGED2 (ClinVar, Single submitter, 3 submitters; last evaluated 2025-12-18). AlphaMissense: likely benign (0.0812); Ultra-rare (popmax 0.0763%, nfe).

How common is MAGED2 p.Ala577Thr (c.1729G>A) in the general population?

MAGED2 p.Ala577Thr (c.1729G>A) is ultra-rare (popmax 0.0763%, nfe) (gnomAD).

What do computational predictors say about MAGED2 p.Ala577Thr (c.1729G>A)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

MAGED2 p.Ala577Thr

c.1729G>A · rs376899197 · VCV1206207

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.33	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 0.99	GERP -3.3, phastCons 0.002
Regional constraint	o/e 0.88	unconstrained · MANE · 228 bp · p 0.34 · regional, not allelic
Overall
CADD	10.62	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 0.0763% European (non-Finnish) · 666/873,096 alleles

Filtering AF 0.0714% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0695%

Overall 0.0618% 721/1,167,171 alleles · ultra-rare exomes 656/1,054,440 · genomes 65/112,731 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0763%	1,311
Remaining individualsnot grpmax-eligible	0.0654%	1,530
African / African-American	0.0196%	5,090
Admixed American	0.0154%	6,474
Finnishnot grpmax-eligible	0.00912%	10,962
East Asian	0.0065%	15,389
South Asian	0.0038%	26,345

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.Ala577Thr
Coding: c.1729G>A
MANE Select: NM_177433
dbSNP: rs376899197
Type: single nucleotide variant
Location: chrX:54815590 (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-ala577thr (accessed [today's date]).

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