Is MAGI2 p.Pro511His (c.1532C>A) pathogenic?

MAGI2 p.Pro511His (c.1532C>A) is classified Uncertain significance in MAGI2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-07). AlphaMissense: ambiguous (0.4043); Very rare (popmax 0.00271%, nfe); Associated with nephrotic syndrome 15.

What condition is associated with MAGI2 p.Pro511His (c.1532C>A)?

MAGI2 p.Pro511His (c.1532C>A) is associated with nephrotic syndrome 15 (ClinVar).

How common is MAGI2 p.Pro511His (c.1532C>A) in the general population?

MAGI2 p.Pro511His (c.1532C>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about MAGI2 p.Pro511His (c.1532C>A)?

AlphaMissense predicts ambiguous (score 0.4043) — an in-silico prediction, not a clinical call.

MAGI2 p.Pro511His

c.1532C>A · VCV3292711

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4043 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Conditions

nephrotic syndrome 15

Computational evidence

Protein change
AlphaMissense	0.4043	ambiguous
REVEL	0.439	indeterminate
SaProt	LLR -16.83	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 376 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	26.9	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 0.00271% European (non-Finnish) · 32/1,179,968 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,613,798 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,874
African / African-American	0.00267%	37,452

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: MAGI2
Protein: p.Pro511His
Coding: c.1532C>A
MANE Select: NM_012301
Type: single nucleotide variant
Location: chr7:78256458 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB

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

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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-pro511his (accessed [today's date]).

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