MAGI2 p.Pro638=
c.1914T>G · rs746306479 · VCV2892544
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00915%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP -1, phastCons 1 |
| Overall | ||
| CADD | 9.265 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00915%
European (non-Finnish) · 108/1,179,918 alleles
Filtering AF
0.00774%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00719%
Overall
0.00688%
111/1,613,642 alleles · very rare
exomes 108/1,461,454 · genomes 3/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00915% | 10,925 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| Admixed American | 0.00167% | 59,966 |
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.Pro638=
- Coding
- c.1914T>G
- MANE Select
- NM_012301
- dbSNP
- rs746306479
- Type
- single nucleotide variant
- Location
- chr7:78256076 (GRCh38)
- Gene constraint
- LOEUF 0.369 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 61.10 · 5 PDB
- Residue 638
- the pdz 3 domain
Similar variants
- MAGI2 p.Ala1028Val Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala1247Thr Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala1271Thr Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala1453Thr Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala274Thr Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala620Gly Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala809Ser Uncertain significance ★★ ⚠ same type
- MAGI2 p.Ala899Pro Uncertain significance ★★ ⚠ same type
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-pro638 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown