Is MAGI2 p.Pro908Arg (c.2723C>G) pathogenic?

MAGI2 p.Pro908Arg (c.2723C>G) is classified Uncertain significance in MAGI2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-11-04). AlphaMissense: likely benign (0.1411); Ultra-rare (popmax 0.0748%, nfe); Associated with nephrotic syndrome 15.

What condition is associated with MAGI2 p.Pro908Arg (c.2723C>G)?

MAGI2 p.Pro908Arg (c.2723C>G) is associated with nephrotic syndrome 15 (ClinVar).

How common is MAGI2 p.Pro908Arg (c.2723C>G) in the general population?

MAGI2 p.Pro908Arg (c.2723C>G) is ultra-rare (popmax 0.0748%, nfe) (gnomAD).

What do computational predictors say about MAGI2 p.Pro908Arg (c.2723C>G)?

AlphaMissense predicts likely benign (score 0.1411) — an in-silico prediction, not a clinical call.

MAGI2 p.Pro908Arg

c.2723C>G · rs150080418 · VCV498637

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1411 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0748%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

nephrotic syndrome 15

Computational evidence

Protein change
AlphaMissense	0.1411	likely benign
REVEL	0.115	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 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 376 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0748% European (non-Finnish) · 882/1,179,408 alleles

Filtering AF 0.0707% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.069%

Overall 0.059% 951/1,612,838 alleles · ultra-rare exomes 898/1,460,508 · genomes 53/152,330 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0748%	1,337
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Middle Eastern	0.033%	3,030
Finnishnot grpmax-eligible	0.0187%	5,337
East Asian	0.0134%	7,476
Admixed American	0.0134%	7,483
African / African-American	0.00799%	12,512
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598

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.Pro908Arg
Coding: c.2723C>G
MANE Select: NM_012301
dbSNP: rs150080418
Type: single nucleotide variant
Location: chr7:78160147 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB
Residue 908: 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.Pro908His Uncertain significance ★★ ⚠ same residue
MAGI2 p.Pro908Ala Uncertain significance ★ ⚠ same residue
MAGI2 p.Pro908Leu Uncertain significance ★ ⚠ same residue
MAGI2 p.Pro908Thr Uncertain significance ★ ⚠ same residue
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

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-pro908arg (accessed [today's date]).

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