Is MMP2 p.Ser32= (c.96G>T) pathogenic?

MMP2 p.Ser32= (c.96G>T) is classified Conflicting classifications of pathogenicity in MMP2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-19). Ultra-rare (popmax 0.0965%, nfe); Associated with multicentric osteolysis-nodulosis-arthropathy spectrum.

What condition is associated with MMP2 p.Ser32= (c.96G>T)?

MMP2 p.Ser32= (c.96G>T) is associated with multicentric osteolysis-nodulosis-arthropathy spectrum (ClinVar).

How common is MMP2 p.Ser32= (c.96G>T) in the general population?

MMP2 p.Ser32= (c.96G>T) is ultra-rare (popmax 0.0965%, nfe) (gnomAD).

MMP2 p.Ser32=

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

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

c.96G>T · rs146220690 · VCV729361

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 0.0965%, nfe)

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 0.056	GERP -4, phastCons 0.69
Overall
CADD	12.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0965% European (non-Finnish) · 1,139/1,179,992 alleles

Filtering AF 0.0918% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0899%

Overall 0.0725% 1,170/1,613,392 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0965%	1,036
Remaining individualsnot grpmax-eligible	0.0208%	4,806
Middle Eastern	0.0164%	6,084
African / African-American	0.012%	8,326
Admixed American	0.00833%	12,000
East Asian	0.00446%	22,434
Finnishnot grpmax-eligible	0.00158%	63,444

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.Ser32=
Coding: c.96G>T
MANE Select: NM_004530
dbSNP: rs146220690
Type: single nucleotide variant
Location: chr16:55479575 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB

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-ser32 (accessed [today's date]).

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