Is MAGED2 p.Ser84= (c.252A>G) pathogenic?

MAGED2 p.Ser84= (c.252A>G) is classified Benign in MAGED2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 63.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Bartter disease type 5.

What condition is associated with MAGED2 p.Ser84= (c.252A>G)?

MAGED2 p.Ser84= (c.252A>G) is associated with Bartter disease type 5 (ClinVar).

How is Bartter syndrome inherited?

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

MAGED2 p.Ser84=

Q: How common is MAGED2 p.Ser84= (c.252A>G) in the general population?

MAGED2 p.Ser84= (c.252A>G) is common (popmax 63.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.252A>G · rs1043031 · VCV1244776

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 63.4%, eas) — too common for a highly-penetrant pathogenic allele

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 2.6	GERP 0.7, phastCons 0.13
Overall
CADD	9.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.4% East Asian · 21,089/33,279 alleles

Filtering AF 62.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 62.4%

Overall 35.2% 421,123/1,196,048 alleles · common exomes 383,735/1,086,329 · genomes 37,388/109,719 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	63.4%	2
Finnishnot grpmax-eligible	40.2%	2
South Asian	38.8%	3
Ashkenazi Jewishnot grpmax-eligible	37.8%	3
Remaining individualsnot grpmax-eligible	34.8%	3
Admixed American	34.2%	3
European (non-Finnish)	34%	3
African / African-American	30.3%	3
Middle Eastern	29.7%	3
Amishnot grpmax-eligible	10.8%	9

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.Ser84=
Coding: c.252A>G
MANE Select: NM_177433
dbSNP: rs1043031
Type: single nucleotide variant
Location: chrX:54809928 (GRCh38)
Structure: AlphaFold pLDDT 59.89
Residue 84: 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.Ser84Leu Uncertain significance ★ ⚠ same residue
MAGED2 p.Pro153Ser Uncertain significance ★★ ⚠ same condition
MAGED2 p.Ala208= Benign ★★ same condition
MAGED2 p.Pro272= Benign/Likely benign ★★ same condition
MAGED2 p.Ser327= 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

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-ser84 (accessed [today's date]).

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