Is MAGI2 p.Pro1249= (c.3747A>C) pathogenic?

MAGI2 p.Pro1249= (c.3747A>C) is classified Uncertain significance in MAGI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-29). Absent from gnomAD v4.1; Associated with nephrotic syndrome 15.

What condition is associated with MAGI2 p.Pro1249= (c.3747A>C)?

MAGI2 p.Pro1249= (c.3747A>C) is associated with nephrotic syndrome 15 (ClinVar).

How common is MAGI2 p.Pro1249= (c.3747A>C) in the general population?

MAGI2 p.Pro1249= (c.3747A>C) is absent from gnomAD v4.1 (gnomAD).

MAGI2 p.Pro1249=

c.3747A>C · VCV3594813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

nephrotic syndrome 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.06	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.7, phastCons 1
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

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: MAGI2
Protein: p.Pro1249=
Coding: c.3747A>C
MANE Select: NM_012301
Type: single nucleotide variant
Location: chr7:78019936 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB
Residue 1249: the 'disordered' region

Full MAGI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephrotic syndrome 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAGI2 p.Ala1028Val Uncertain significance ★★ ⚠ same condition
MAGI2 p.Ala1247Thr Uncertain significance ★★ ⚠ same condition
MAGI2 p.Ala1271Thr Uncertain significance ★★ ⚠ same condition
MAGI2 p.Ala1453Thr Uncertain significance ★★ ⚠ same condition
MAGI2 p.Ala620Gly Uncertain significance ★★ ⚠ same condition
MAGI2 p.Ala899Pro Uncertain significance ★★ ⚠ same condition
MAGI2 p.Arg1370Pro Uncertain significance ★★ ⚠ same condition
MAGI2 p.Arg408Gln Uncertain significance ★★ ⚠ 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/magi2-p-pro1249 (accessed [today's date]).

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