MMP13 p.Phe424=
c.1272C>T · rs782542049 · VCV2914546
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0114%, 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 1.6 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 7.292 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0114%
European (non-Finnish) · 133/1,171,624 alleles
Filtering AF
0.00976%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00911%
Overall
0.00873%
140/1,603,618 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0114% | 8,809 |
| Admixed American | 0.00667% | 14,995 |
| Remaining individualsnot grpmax-eligible | 0.00483% | 20,709 |
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
- MMP13
- Protein
- p.Phe424=
- Coding
- c.1272C>T
- MANE Select
- NM_002427
- dbSNP
- rs782542049
- Type
- single nucleotide variant
- Location
- chr11:102945689 (GRCh38)
- Gene constraint
- LOEUF 1.067 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.00 · 49 PDB
- Residue 424
- a disulfide bond; the 'interaction with collagen' region
Similar variants
- MMP13 c.1052-1G>C Pathogenic/Likely pathogenic ★★ same type
- MMP13 p.Trp207Gly Pathogenic/Likely pathogenic ★★ same type
- MMP13 p.Ala221Val Uncertain significance ★★ ⚠ same type
- MMP13 p.Ala318Val Uncertain significance ★★ ⚠ same type
- MMP13 p.Ala356Val Uncertain significance ★★ ⚠ same type
- MMP13 p.Arg155Ile Uncertain significance ★★ ⚠ same type
- MMP13 p.Arg310Cys Uncertain significance ★★ ⚠ same type
- MMP13 p.Arg310His 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/mmp13-p-phe424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown