Is MMP2 p.Ala366= (c.1098C>T) pathogenic?

MMP2 p.Ala366= (c.1098C>T) is classified Benign in MMP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 5.64%, afr) — too common for a highly-penetrant pathogenic allele; Associated with multicentric osteolysis-nodulosis-arthropathy spectrum.

What condition is associated with MMP2 p.Ala366= (c.1098C>T)?

MMP2 p.Ala366= (c.1098C>T) is associated with multicentric osteolysis-nodulosis-arthropathy spectrum (ClinVar).

MMP2 p.Ala366=

Q: How common is MMP2 p.Ala366= (c.1098C>T) in the general population?

MMP2 p.Ala366= (c.1098C>T) is common (popmax 5.64%, afr) — 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.1098C>T · rs16955236 · VCV319754

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.64%, afr) — 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 -4
Overall
CADD	1.998	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.64% African / African-American · 4,231/75,010 alleles

Filtering AF 5.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.44%

Overall 0.936% 15,111/1,614,142 alleles · common exomes 11,837/1,461,880 · genomes 3,274/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.64%	18
Ashkenazi Jewishnot grpmax-eligible	4.08%	24
Middle Eastern	2.23%	45
Remaining individualsnot grpmax-eligible	1.28%	78
Admixed American	0.841%	119
European (non-Finnish)	0.632%	158
Finnishnot grpmax-eligible	0.598%	167
South Asian	0.436%	229

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.Ala366=
Coding: c.1098C>T
MANE Select: NM_004530
dbSNP: rs16955236
Type: single nucleotide variant
Location: chr16:55489742 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 366: the 'collagen-binding' region; the fibronectin type-ii 3 domain

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-ala366 (accessed [today's date]).

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