MMP14 p.Pro259=
c.777C>G · rs2236302 · VCV1232955
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 28.9%, afr) — too common for a highly-penetrant pathogenic allele
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 -0.82 | GERP -5, phastCons 0.003 |
| Overall | ||
| CADD | 5.385 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
28.9%
African / African-American · 21,654/74,886 alleles
Filtering AF
28.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 28.5%
Overall
11.4%
183,158/1,613,690 alleles · common
exomes 159,160/1,461,632 · genomes 23,998/152,058 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 28.9% | 3 |
| Admixed American | 14.8% | 7 |
| East Asian | 12.1% | 8 |
| Remaining individualsnot grpmax-eligible | 11.8% | 8 |
| Middle Eastern | 10.9% | 9 |
| Finnishnot grpmax-eligible | 10.7% | 9 |
| European (non-Finnish) | 10.4% | 10 |
| Ashkenazi Jewishnot grpmax-eligible | 10.4% | 10 |
| South Asian | 6.68% | 15 |
| Amishnot grpmax-eligible | 3.62% | 28 |
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
- MMP14
- Protein
- p.Pro259=
- Coding
- c.777C>G
- MANE Select
- NM_004995
- dbSNP
- rs2236302
- Type
- single nucleotide variant
- Location
- chr14:22843345 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 12 PDB
- Residue 259
- a β-strand
Similar variants
- MMP14 c.850+2C>T Uncertain significance ★★ same type
- MMP14 p.Ala165Asp Uncertain significance ★★ ⚠ same type
- MMP14 p.Ala366Val Uncertain significance ★★ ⚠ same type
- MMP14 p.Ala539Thr Uncertain significance ★★ ⚠ same type
- MMP14 p.Ala539Val Uncertain significance ★★ ⚠ same type
- MMP14 p.Arg168Cys Uncertain significance ★★ ⚠ same type
- MMP14 p.Arg343Trp Uncertain significance ★★ ⚠ same type
- MMP14 p.Arg362Gln 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/mmp14-p-pro259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown