Is MMP14 p.Phe467Leu (c.1401C>G) pathogenic?

MMP14 p.Phe467Leu (c.1401C>G) is classified Uncertain significance in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). AlphaMissense: likely pathogenic (0.9709); Very rare (popmax 0.00336%, amr).

How common is MMP14 p.Phe467Leu (c.1401C>G) in the general population?

MMP14 p.Phe467Leu (c.1401C>G) is very rare (popmax 0.00336%, amr) (gnomAD).

What do computational predictors say about MMP14 p.Phe467Leu (c.1401C>G)?

AlphaMissense predicts likely pathogenic (score 0.9709) — an in-silico prediction, not a clinical call.

MMP14 p.Phe467Leu

c.1401C>G · rs1168823031 · VCV2070900

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9709 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00336%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9709	likely pathogenic
REVEL	0.176	moderately benign-leaning
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,683 bp · p 0.003 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.00336% Admixed American · 2/59,460 alleles

Filtering AF 0.000558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000209%

Overall 0.000249% 4/1,608,880 alleles · very rare exomes 3/1,456,772 · genomes 1/152,108 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00336%	29,730
Remaining individualsnot grpmax-eligible	0.00161%	62,254
European (non-Finnish)	8.49e-05%	1,177,224

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.Phe467Leu
Coding: c.1401C>G
MANE Select: NM_004995
dbSNP: rs1168823031
Type: single nucleotide variant
Location: chr14:22845350 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 12 PDB
Residue 467: a β-strand

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-phe467leu (accessed [today's date]).

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