Is MMP2 p.Pro43Ser (c.127C>T) pathogenic?

MMP2 p.Pro43Ser (c.127C>T) is classified Uncertain significance in MMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-27). AlphaMissense: likely benign (0.0896); Very rare (popmax 0.00223%, eas).

How common is MMP2 p.Pro43Ser (c.127C>T) in the general population?

MMP2 p.Pro43Ser (c.127C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MMP2 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

MMP2 p.Pro43Ser

c.127C>T · rs1352361846 · VCV1509324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -8.88	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 5.8	GERP 0.73, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 4,680 bp · p 0.52 · regional, not allelic
Overall
CADD	22.2	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 0.00223% East Asian · 1/44,864 alleles

Overall 0.000124% 2/1,613,802 alleles · very rare exomes 2/1,461,458 · genomes 0/152,344 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,864
European (non-Finnish)	8.47e-05%	1,180,011

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.Pro43Ser
Coding: c.127C>T
MANE Select: NM_004530
dbSNP: rs1352361846
Type: single nucleotide variant
Location: chr16:55479606 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 43: an α-helix

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

Similar variants

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
MMP2 p.Arg296His 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-pro43ser (accessed [today's date]).

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