Is MMP14 p.Val445Met (c.1333G>A) pathogenic?

MMP14 p.Val445Met (c.1333G>A) is classified Uncertain significance in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-23). AlphaMissense: ambiguous (0.496); Absent from gnomAD v4.1.

How common is MMP14 p.Val445Met (c.1333G>A) in the general population?

MMP14 p.Val445Met (c.1333G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MMP14 p.Val445Met (c.1333G>A)?

AlphaMissense predicts ambiguous (score 0.496) — an in-silico prediction, not a clinical call.

MMP14 p.Val445Met

c.1333G>A · rs1343929448 · VCV1908449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.496 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.496	ambiguous
REVEL	0.234	benign-leaning
SaProt	LLR -10.84	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,683 bp · p 0.003 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

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: MMP14
Protein: p.Val445Met
Coding: c.1333G>A
MANE Select: NM_004995
dbSNP: rs1343929448
Type: single nucleotide variant
Location: chr14:22845282 (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

Similar variants

MMP14 c.850+2C>T Uncertain significance ★★ same type
MMP14 p.Ala165Asp Uncertain significance ★★ ⚠ same type
MMP14 p.Ala366Val Uncertain significance ★★ ⚠ same type
MMP14 p.Ala539Thr Uncertain significance ★★ ⚠ same type
MMP14 p.Ala539Val Uncertain significance ★★ ⚠ same type
MMP14 p.Arg168Cys Uncertain significance ★★ ⚠ same type
MMP14 p.Arg343Trp Uncertain significance ★★ ⚠ same type
MMP14 p.Arg362Gln 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/mmp14-p-val445met (accessed [today's date]).

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