Is MMP2 p.Val620= (c.1860C>T) pathogenic?

MMP2 p.Val620= (c.1860C>T) is classified Conflicting classifications of pathogenicity in MMP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-25). Ultra-rare (popmax 0.0683%, amr); Associated with multicentric osteolysis-nodulosis-arthropathy spectrum.

What condition is associated with MMP2 p.Val620= (c.1860C>T)?

MMP2 p.Val620= (c.1860C>T) is associated with multicentric osteolysis-nodulosis-arthropathy spectrum (ClinVar).

How common is MMP2 p.Val620= (c.1860C>T) in the general population?

MMP2 p.Val620= (c.1860C>T) is ultra-rare (popmax 0.0683%, amr) (gnomAD).

MMP2 p.Val620=

Q: How is Multicentric osteolysis-nodulosis-arthropathy spectrum inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1860C>T · rs139606653 · VCV714021

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0683%, amr)

Conditions

multicentric osteolysis-nodulosis-arthropathy spectrum

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 -5.2	GERP -5.1
Overall
CADD	0.257	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0683% Admixed American · 41/60,032 alleles

Filtering AF 0.0517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.0323% 522/1,613,836 alleles · ultra-rare exomes 481/1,461,460 · genomes 41/152,376 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0683%	1,464
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
European (non-Finnish)	0.0373%	2,682
Remaining individualsnot grpmax-eligible	0.0304%	3,289
African / African-American	0.00932%	10,725
East Asian	0.00223%	44,880

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.Val620=
Coding: c.1860C>T
MANE Select: NM_004530
dbSNP: rs139606653
Type: single nucleotide variant
Location: chr16:55502869 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 620: a β-strand; the 'required for inhibitor timp2 binding' region

Full MMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multicentric osteolysis-nodulosis-arthropathy spectrum — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multicentric osteolysis-nodulosis-arthropathy spectrum (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MMP2 p.Val620Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MMP2 p.Val620Phe Uncertain significance ★ ⚠ same residue
MMP2 p.Cys102Ter Pathogenic/Likely pathogenic ★★ same condition
MMP2 p.Tyr244Ter Pathogenic ★★ same condition
MMP2 c.380+6G>A Uncertain significance ★★ same condition
MMP2 p.Ala545Val Uncertain significance ★★ ⚠ same condition
MMP2 p.Arg115Leu Uncertain significance ★★ same condition
MMP2 p.Arg296His Uncertain significance ★★ ⚠ same condition

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-val620 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown