Is MMP14 p.Pro3Ala (c.7C>G) pathogenic?

MMP14 p.Pro3Ala (c.7C>G) is classified Uncertain significance in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). AlphaMissense: likely benign (0.0429); Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with MMP14 p.Pro3Ala (c.7C>G)?

MMP14 p.Pro3Ala (c.7C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MMP14 p.Pro3Ala (c.7C>G) in the general population?

MMP14 p.Pro3Ala (c.7C>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about MMP14 p.Pro3Ala (c.7C>G)?

AlphaMissense predicts likely benign (score 0.0429) — an in-silico prediction, not a clinical call.

MMP14 p.Pro3Ala

c.7C>G · VCV4055727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0429	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP 1, phastCons 0.93
Regional constraint	o/e 0.92	unconstrained · MANE · 4,675 bp · p 0.59 · regional, not allelic
Overall
CADD	19.3	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 0.00224% East Asian · 1/44,608 alleles

Overall 0.000125% 2/1,601,868 alleles · very rare exomes 1/1,449,760 · genomes 1/152,108 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,608
Admixed American	0.00169%	59,144

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: MMP14
Protein: p.Pro3Ala
Coding: c.7C>G
MANE Select: NM_004995
Type: single nucleotide variant
Location: chr14:22836824 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 12 PDB

Full MMP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MMP14 p.Pro3Leu Uncertain significance ★ ⚠ same residue
MMP14 p.Ala165Asp Uncertain significance ★★ ⚠ same condition
MMP14 p.Ala366Val Uncertain significance ★★ ⚠ same condition
MMP14 p.Ala539Thr Uncertain significance ★★ ⚠ same condition
MMP14 p.Ala539Val Uncertain significance ★★ ⚠ same condition
MMP14 p.Arg168Cys Uncertain significance ★★ ⚠ same condition
MMP14 p.Arg343Trp Uncertain significance ★★ ⚠ same condition
MMP14 p.Arg362Gln 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/mmp14-p-pro3ala (accessed [today's date]).

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