Is MAGED2 p.Pro272= (c.816A>G) pathogenic?

MAGED2 p.Pro272= (c.816A>G) is classified Benign/Likely benign in MAGED2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). Low-frequency (popmax 1.3%, afr); Associated with Bartter disease type 5.

What condition is associated with MAGED2 p.Pro272= (c.816A>G)?

MAGED2 p.Pro272= (c.816A>G) is associated with Bartter disease type 5 (ClinVar).

How common is MAGED2 p.Pro272= (c.816A>G) in the general population?

MAGED2 p.Pro272= (c.816A>G) is low-frequency (popmax 1.3%, afr) (gnomAD).

How is Bartter syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MAGED2 p.Pro272=

c.816A>G · rs111542041 · VCV786394

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, afr)

Conditions

Bartter disease type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.46, phastCons 0.13
Overall
CADD	11.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.3% African / African-American · 735/56,621 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.19%

Overall 0.0702% 838/1,194,425 alleles · low-frequency exomes 410/1,082,124 · genomes 428/112,301 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.3%	77
Remaining individualsnot grpmax-eligible	0.109%	918
Admixed American	0.0908%	1,101
Middle Eastern	0.0467%	2,141
European (non-Finnish)	0.00113%	88,662

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.Pro272=
Coding: c.816A>G
MANE Select: NM_177433
dbSNP: rs111542041
Type: single nucleotide variant
Location: chrX:54811099 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 272: the 'disordered' region

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

Disease context

Bartter disease type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bartter syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

MAGED2 p.Pro153Ser Uncertain significance ★★ ⚠ same condition
MAGED2 p.Ala208= Benign ★★ same condition
MAGED2 p.Ser327= Benign ★★ same condition
MAGED2 p.Ser84= Benign ★★ same condition
MAGED2 p.Thr132= Benign ★★ same condition
MAGED2 c.1386+1G>A Likely pathogenic ★ same condition
MAGED2 p.Arg446Cys Likely pathogenic ★ same condition
MAGED2 p.Gln88Ter Pathogenic ★ 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-pro272 (accessed [today's date]).

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