Is MMP14 p.Arg339= (c.1017C>T) pathogenic?

MMP14 p.Arg339= (c.1017C>T) is classified Likely benign in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Ultra-rare (popmax 0.024%, afr).

How common is MMP14 p.Arg339= (c.1017C>T) in the general population?

MMP14 p.Arg339= (c.1017C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

MMP14 p.Arg339=

c.1017C>T · rs144898101 · VCV2909015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -3.7, phastCons 0.99
Overall
CADD	9.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/74,920 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0013% 21/1,614,040 alleles · ultra-rare exomes 9/1,461,838 · genomes 12/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,162
Finnishnot grpmax-eligible	0.00469%	21,343

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.Arg339=
Coding: c.1017C>T
MANE Select: NM_004995
dbSNP: rs144898101
Type: single nucleotide variant
Location: chr14:22844376 (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 p.Arg339His Uncertain significance ★ ⚠ 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-arg339 (accessed [today's date]).

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