Is MMP14 p.Arg9His (c.26G>A) pathogenic?

MMP14 p.Arg9His (c.26G>A) is classified Uncertain significance in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-13). AlphaMissense: likely benign (0.1693); No allele count reported in gnomAD v4.1 (AN 1,612,728).

How common is MMP14 p.Arg9His (c.26G>A) in the general population?

MMP14 p.Arg9His (c.26G>A) is no allele count reported in gnomAD v4.1 (AN 1,612,728) (gnomAD).

What do computational predictors say about MMP14 p.Arg9His (c.26G>A)?

AlphaMissense predicts likely benign (score 0.1693) — an in-silico prediction, not a clinical call.

MMP14 p.Arg9His

c.26G>A · rs2502055629 · VCV2111040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1693 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,728)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1693	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -8.51	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 7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,675 bp · p 0.59 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,612,728). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MMP14
Protein: p.Arg9His
Coding: c.26G>A
MANE Select: NM_004995
dbSNP: rs2502055629
Type: single nucleotide variant
Location: chr14:22836843 (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.Arg9Ser 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-arg9his (accessed [today's date]).

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