Is MMP14 p.Ile233Val (c.697A>G) pathogenic?

MMP14 p.Ile233Val (c.697A>G) is classified Benign in MMP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.1142); Low-frequency (popmax 2.4%, afr).

How common is MMP14 p.Ile233Val (c.697A>G) in the general population?

MMP14 p.Ile233Val (c.697A>G) is low-frequency (popmax 2.4%, afr) (gnomAD).

What do computational predictors say about MMP14 p.Ile233Val (c.697A>G)?

AlphaMissense predicts likely benign (score 0.1142) — an in-silico prediction, not a clinical call.

MMP14 p.Ile233Val

c.697A>G · rs17884841 · VCV770238

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1142 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.4%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1142	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -5.09	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 2.2	GERP -5, phastCons 0.89
Regional constraint	o/e 0.63	unconstrained · MANE · 1,799 bp · p 5.5e-10 · regional, not allelic
Overall
CADD	13.71	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 2.4% African / African-American · 1,803/75,018 alleles

Filtering AF 2.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.27%

Overall 0.132% 2,124/1,613,450 alleles · low-frequency exomes 1,080/1,461,186 · genomes 1,044/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.4%	42
Admixed American	0.22%	455
Remaining individualsnot grpmax-eligible	0.181%	553
Middle Eastern	0.149%	673
South Asian	0.0143%	7,004
European (non-Finnish)	0.00449%	22,256
Finnishnot grpmax-eligible	0.00156%	63,914

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.Ile233Val
Coding: c.697A>G
MANE Select: NM_004995
dbSNP: rs17884841
Type: single nucleotide variant
Location: chr14:22843265 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 12 PDB
Residue 233: a UniProt-annotated variant site (in); an α-helix

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

Similar variants

MMP14 p.Ile233= Likely benign ★ same residue
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

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-ile233val (accessed [today's date]).

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