Is MMP2 p.Phe57Ser (c.170T>C) pathogenic?

MMP2 p.Phe57Ser (c.170T>C) is classified Uncertain significance in MMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-22). AlphaMissense: likely pathogenic (0.9665); Absent from gnomAD v4.1.

How common is MMP2 p.Phe57Ser (c.170T>C) in the general population?

MMP2 p.Phe57Ser (c.170T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MMP2 p.Phe57Ser (c.170T>C)?

AlphaMissense predicts likely pathogenic (score 0.9665) — an in-silico prediction, not a clinical call.

MMP2 p.Phe57Ser

c.170T>C · rs2543503310 · VCV2089123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9665 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9665	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -11.74	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 4,680 bp · p 0.52 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Phe57Ser
Coding: c.170T>C
MANE Select: NM_004530
dbSNP: rs2543503310
Type: single nucleotide variant
Location: chr16:55482925 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.31 · 14 PDB
Residue 57: 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-phe57ser (accessed [today's date]).

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