MMP14 p.His239=
c.717C>T · rs548260059 · VCV1905112
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0535%, eas)
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 -9.1 | GERP -5 |
| Overall | ||
| CADD | 0.475 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0535%
East Asian · 24/44,874 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0313%
Overall
0.00341%
55/1,613,926 alleles · ultra-rare
exomes 49/1,461,640 · genomes 6/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0535% | 1,870 |
| South Asian | 0.011% | 9,107 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| Admixed American | 0.00167% | 60,014 |
| African / African-American | 0.00133% | 75,042 |
| European (non-Finnish) | 0.00127% | 78,661 |
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.His239=
- Coding
- c.717C>T
- MANE Select
- NM_004995
- dbSNP
- rs548260059
- Type
- single nucleotide variant
- Location
- chr14:22843285 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 12 PDB
- Residue 239
- a binding site; an α-helix
Similar variants
- MMP14 p.His239Gln Uncertain significance ★ ⚠ same residue
- 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
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-his239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown