Is MAGI2 p.Asp990= (c.2970C>T) pathogenic?

MAGI2 p.Asp990= (c.2970C>T) is classified Uncertain significance in MAGI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-07). Very rare (popmax 0.00322%, nfe); Associated with nephrotic syndrome 15.

What condition is associated with MAGI2 p.Asp990= (c.2970C>T)?

MAGI2 p.Asp990= (c.2970C>T) is associated with nephrotic syndrome 15 (ClinVar).

How common is MAGI2 p.Asp990= (c.2970C>T) in the general population?

MAGI2 p.Asp990= (c.2970C>T) is very rare (popmax 0.00322%, nfe) (gnomAD).

MAGI2 p.Asp990=

c.2970C>T · VCV3594832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

Conditions

nephrotic syndrome 15

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 5.7	GERP 2, phastCons 1
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 38/1,180,030 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00242% 39/1,614,062 alleles · very rare exomes 37/1,461,882 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00322%	31,053
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Asp990=
Coding: c.2970C>T
MANE Select: NM_012301
Type: single nucleotide variant
Location: chr7:78135082 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.10 · 5 PDB
Residue 990: an α-helix; the pdz 5 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

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-asp990 (accessed [today's date]).

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