Is MMP2 p.Phe602= (c.1806C>T) pathogenic?

MMP2 p.Phe602= (c.1806C>T) is classified Benign in MMP2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 45.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with multicentric osteolysis-nodulosis-arthropathy spectrum.

What condition is associated with MMP2 p.Phe602= (c.1806C>T)?

MMP2 p.Phe602= (c.1806C>T) is associated with multicentric osteolysis-nodulosis-arthropathy spectrum (ClinVar).

MMP2 p.Phe602=

Q: How common is MMP2 p.Phe602= (c.1806C>T) in the general population?

MMP2 p.Phe602= (c.1806C>T) is common (popmax 45.7%, 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.1806C>T · rs14070 · VCV319768

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 45.7%, 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 0.18	GERP -2.8, phastCons 0.97
Overall
CADD	8.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.7% European (non-Finnish) · 539,045/1,178,668 alleles

Filtering AF 45.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.6%

Overall 42.7% 688,740/1,612,436 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	65.2%	2
European (non-Finnish)grpmax	45.7%	2
Admixed American	42.5%	2
Remaining individualsnot grpmax-eligible	41.3%	2
Middle Eastern	40.6%	2
Finnishnot grpmax-eligible	40.1%	2
Ashkenazi Jewishnot grpmax-eligible	39.3%	3
South Asian	35.6%	3
East Asian	25.8%	4
African / African-American	18.7%	5

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe602=
Coding: c.1806C>T
MANE Select: NM_004530
dbSNP: rs14070
Type: single nucleotide variant
Location: chr16:55502815 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 602: 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.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
MMP2 p.Asp382Asn 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-phe602 (accessed [today's date]).

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