Is MAGI2 p.Val150Phe (c.448G>T) pathogenic?

MAGI2 p.Val150Phe (c.448G>T) is classified Uncertain significance in MAGI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-18). AlphaMissense: likely pathogenic (0.8621); Very rare (popmax 0.00137%, afr); Associated with nephrotic syndrome 15.

What condition is associated with MAGI2 p.Val150Phe (c.448G>T)?

MAGI2 p.Val150Phe (c.448G>T) is associated with nephrotic syndrome 15 (ClinVar).

How common is MAGI2 p.Val150Phe (c.448G>T) in the general population?

MAGI2 p.Val150Phe (c.448G>T) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about MAGI2 p.Val150Phe (c.448G>T)?

AlphaMissense predicts likely pathogenic (score 0.8621) — an in-silico prediction, not a clinical call.

MAGI2 p.Val150Phe

c.448G>T · VCV3594901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

nephrotic syndrome 15

Computational evidence

Protein change
AlphaMissense	0.8621	likely pathogenic
REVEL	0.521	indeterminate
SaProt	LLR -12.90	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 932 kb · p 4e-09 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00137% African / African-American · 1/73,180 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000316% 5/1,581,184 alleles · very rare exomes 5/1,428,980 · genomes 0/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,180
European (non-Finnish)	0.000344%	290,931

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.Val150Phe
Coding: c.448G>T
MANE Select: NM_012301
Type: single nucleotide variant
Location: chr7:78627210 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB
Residue 150: the guanylate kinase-like domain

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.Ala620Gly Uncertain significance ★★ ⚠ same condition
MAGI2 p.Ala899Pro Uncertain significance ★★ ⚠ same condition
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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-val150phe (accessed [today's date]).

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