Is MMP14 p.Ala64Val (c.191C>T) pathogenic?

MMP14 p.Ala64Val (c.191C>T) is classified Uncertain significance in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely pathogenic (0.9715); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with MMP14 p.Ala64Val (c.191C>T)?

MMP14 p.Ala64Val (c.191C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MMP14 p.Ala64Val (c.191C>T) in the general population?

MMP14 p.Ala64Val (c.191C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MMP14 p.Ala64Val (c.191C>T)?

AlphaMissense predicts likely pathogenic (score 0.9715) — an in-silico prediction, not a clinical call.

MMP14 p.Ala64Val

c.191C>T · rs1401887689 · VCV2286109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9715 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9715	likely pathogenic
REVEL	0.421	indeterminate
SaProt	LLR -11.48	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,799 bp · p 5.5e-10 · regional, not allelic
Overall
CADD	28.5	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

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Overall 0.000124% 2/1,614,028 alleles · very rare exomes 1/1,461,798 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
European (non-Finnish)	8.47e-05%	1,180,032

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.Ala64Val
Coding: c.191C>T
MANE Select: NM_004995
dbSNP: rs1401887689
Type: single nucleotide variant
Location: chr14:22841573 (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.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
MMP14 p.Arg513Gln 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-ala64val (accessed [today's date]).

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