Is MMP2 p.Pro614= (c.1842C>G) pathogenic?

MMP2 p.Pro614= (c.1842C>G) is classified Benign in MMP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 11.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with multicentric osteolysis-nodulosis-arthropathy spectrum.

What condition is associated with MMP2 p.Pro614= (c.1842C>G)?

MMP2 p.Pro614= (c.1842C>G) is associated with multicentric osteolysis-nodulosis-arthropathy spectrum (ClinVar).

MMP2 p.Pro614=

Q: How common is MMP2 p.Pro614= (c.1842C>G) in the general population?

MMP2 p.Pro614= (c.1842C>G) is common (popmax 11.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

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

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

c.1842C>G · rs11541998 · VCV319769

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 11.6%, nfe) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -5.1
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.6% European (non-Finnish) · 136,913/1,179,522 alleles

Filtering AF 11.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 9.87% 159,289/1,613,442 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	11.6%	9
Remaining individualsnot grpmax-eligible	9.16%	11
Finnishnot grpmax-eligible	7.97%	13
Amishnot grpmax-eligible	7.47%	13
Admixed American	6.41%	16
Middle Eastern	6.19%	16
Ashkenazi Jewishnot grpmax-eligible	5.1%	20
South Asian	4.75%	21
African / African-American	1.9%	53
East Asian	0.0267%	3,740

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.Pro614=
Coding: c.1842C>G
MANE Select: NM_004530
dbSNP: rs11541998
Type: single nucleotide variant
Location: chr16:55502851 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 614: the 'required for inhibitor timp2 binding' region; a disulfide bond

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.Pro614His 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
MMP2 p.Arg495Gln 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-pro614 (accessed [today's date]).

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