MMP14 p.Ala539=
c.1617G>A · rs781365741 · VCV2729006
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0118%, amr)
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 -14 | GERP -5 |
| Overall | ||
| CADD | 0.017 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0118%
Admixed American · 7/59,236 alleles
Filtering AF
0.0055%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00384%
Overall
0.00335%
54/1,610,306 alleles · ultra-rare
exomes 48/1,458,030 · genomes 6/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0118% | 8,462 |
| European (non-Finnish) | 0.00356% | 28,055 |
| East Asian | 0.00223% | 44,762 |
| South Asian | 0.0022% | 45,404 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,342 |
| African / African-American | 0.00133% | 74,964 |
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.Ala539=
- Coding
- c.1617G>A
- MANE Select
- NM_004995
- dbSNP
- rs781365741
- Type
- single nucleotide variant
- Location
- chr14:22845907 (GRCh38)
- Gene constraint
- LOEUF 0.312 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 81.66 · 12 PDB
Similar variants
- MMP14 p.Ala539Thr Uncertain significance ★★ ⚠ same residue
- MMP14 p.Ala539Val 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.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-ala539 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown