MMP9 p.Pro447=
c.1341T>A · rs747320334 · VCV1440894
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00559%, nfe)
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 0.14 | GERP -0.71, phastCons 0.006 |
| Overall | ||
| CADD | 7.369 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00559%
European (non-Finnish) · 66/1,179,984 alleles
Filtering AF
0.00451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00411%
Overall
0.00421%
68/1,613,900 alleles · very rare
exomes 67/1,461,864 · genomes 1/152,036 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00559% | 17,879 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
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
- MMP9
- Protein
- p.Pro447=
- Coding
- c.1341T>A
- MANE Select
- NM_004994
- dbSNP
- rs747320334
- Type
- single nucleotide variant
- Location
- chr20:46013265 (GRCh38)
- Gene constraint
- LOEUF 1.208 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.96 · 29 PDB
- Residue 447
- the 'disordered' region
Similar variants
- MMP9 p.Cys329Ter Pathogenic/Likely pathogenic ★★ same type
- MMP9 p.Ala144Gly Uncertain significance ★★ same type
- MMP9 p.Ala146Val Uncertain significance ★★ ⚠ same type
- MMP9 p.Ala191Pro Uncertain significance ★★ ⚠ same type
- MMP9 p.Ala417Val Uncertain significance ★★ ⚠ same type
- MMP9 p.Ala593Glu Uncertain significance ★★ ⚠ same type
- MMP9 p.Arg322Trp Uncertain significance ★★ ⚠ same type
- MMP9 p.Arg332Gly 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/mmp9-p-pro447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown