MMP2 p.Val223=
c.669G>A · rs377503997 · VCV1538366
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0454%, afr)
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 1.8 | GERP -4.3, phastCons 1 |
| Overall | ||
| CADD | 6.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0454%
African / African-American · 34/74,916 alleles
Filtering AF
0.0334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0292%
Overall
0.00235%
38/1,614,040 alleles · ultra-rare
exomes 15/1,461,884 · genomes 23/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0454% | 2,203 |
| Admixed American | 0.00333% | 30,003 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| South Asian | 0.0011% | 91,092 |
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
- MMP2
- Protein
- p.Val223=
- Coding
- c.669G>A
- MANE Select
- NM_004530
- dbSNP
- rs377503997
- Type
- single nucleotide variant
- Location
- chr16:55485614 (GRCh38)
- Gene constraint
- LOEUF 0.654 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.31 · 14 PDB
- Residue 223
- the 'collagen-binding' region
Similar variants
- MMP2 p.Cys102Ter Pathogenic/Likely pathogenic ★★ same type
- MMP2 p.Ser396Arg Pathogenic/Likely pathogenic ★★ same type
- MMP2 p.Tyr244Ter Pathogenic ★★ same type
- MMP2 c.380+6G>A Uncertain significance ★★ same type
- MMP2 p.Ala42Ser Uncertain significance ★★ ⚠ same type
- MMP2 p.Ala545Val Uncertain significance ★★ ⚠ same type
- MMP2 p.Arg115Leu Uncertain significance ★★ same type
- MMP2 p.Arg296His 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/mmp2-p-val223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown