Is MMP2 p.Pro13Arg (c.38C>G) pathogenic?

MMP2 p.Pro13Arg (c.38C>G) is classified Uncertain significance in MMP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-28). AlphaMissense: likely benign (0.0921); Very rare (popmax 0.00187%, nfe); Associated with multicentric osteolysis-nodulosis-arthropathy spectrum.

What condition is associated with MMP2 p.Pro13Arg (c.38C>G)?

MMP2 p.Pro13Arg (c.38C>G) is associated with multicentric osteolysis-nodulosis-arthropathy spectrum (ClinVar).

How common is MMP2 p.Pro13Arg (c.38C>G) in the general population?

MMP2 p.Pro13Arg (c.38C>G) is very rare (popmax 0.00187%, nfe) (gnomAD).

What do computational predictors say about MMP2 p.Pro13Arg (c.38C>G)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

MMP2 p.Pro13Arg

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

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

c.38C>G · rs1183157128 · VCV888242

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multicentric osteolysis-nodulosis-arthropathy spectrum

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -2.3
Regional constraint	o/e 0.96	unconstrained · MANE · 4,680 bp · p 0.52 · regional, not allelic
Overall
CADD	10.57	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,175,710 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00152% 22/1,451,446 alleles · very rare

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.Pro13Arg
Coding: c.38C>G
MANE Select: NM_004530
dbSNP: rs1183157128
Type: single nucleotide variant
Location: chr16:55479517 (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.Pro13Ser 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-pro13arg (accessed [today's date]).

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