Is MMP2 p.Pro348Arg (c.1043C>G) pathogenic?

MMP2 p.Pro348Arg (c.1043C>G) is classified Uncertain significance in MMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.3074); Absent from gnomAD v4.1.

How common is MMP2 p.Pro348Arg (c.1043C>G) in the general population?

MMP2 p.Pro348Arg (c.1043C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MMP2 p.Pro348Arg (c.1043C>G)?

AlphaMissense predicts likely benign (score 0.3074) — an in-silico prediction, not a clinical call.

MMP2 p.Pro348Arg

c.1043C>G · rs1962351856 · VCV2002936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3074 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3074	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -0.019, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 20 kb · p 0.13 · regional, not allelic
Overall
CADD	25.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MMP2
Protein: p.Pro348Arg
Coding: c.1043C>G
MANE Select: NM_004530
dbSNP: rs1962351856
Type: single nucleotide variant
Location: chr16:55489687 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 348: an α-helix; the 'collagen-binding' region; the fibronectin type-ii 3 domain

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

Similar variants

MMP2 p.Pro348Leu 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
MMP2 p.Arg115Leu 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-pro348arg (accessed [today's date]).

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