Is MMP2 p.Arg158= (c.474G>T) pathogenic?

MMP2 p.Arg158= (c.474G>T) is classified Likely benign in MMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). Ultra-rare (popmax 0.032%, afr).

How common is MMP2 p.Arg158= (c.474G>T) in the general population?

MMP2 p.Arg158= (c.474G>T) is ultra-rare (popmax 0.032%, afr) (gnomAD).

MMP2 p.Arg158=

c.474G>T · rs144932826 · VCV2418434

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

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 -0.21	GERP -4.1, phastCons 0.038
Overall
CADD	6.893	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/75,046 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00167% 27/1,614,188 alleles · ultra-rare exomes 8/1,461,892 · genomes 19/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,127
European (non-Finnish)	0.000254%	393,351

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.Arg158=
Coding: c.474G>T
MANE Select: NM_004530
dbSNP: rs144932826
Type: single nucleotide variant
Location: chr16:55484109 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 158: the 'collagenase-like 1' region; a β-strand

Full MMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MMP2 p.Arg158Gln Uncertain significance ★ ⚠ same residue
MMP2 p.Arg158Trp Uncertain significance ★ ⚠ same residue
MMP2 p.Cys102Ter Pathogenic/Likely pathogenic ★★ same type
MMP2 p.Ser396Arg Pathogenic/Likely pathogenic ★★ same type
MMP2 p.Tyr244Ter Pathogenic ★★ same type
MMP2 c.380+6G>A Uncertain significance ★★ same type
MMP2 p.Ala42Ser Uncertain significance ★★ ⚠ same type
MMP2 p.Ala545Val Uncertain significance ★★ ⚠ same type

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-arg158 (accessed [today's date]).

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