Is MMP14 p.Arg160His (c.479G>A) pathogenic?

MMP14 p.Arg160His (c.479G>A) is classified Uncertain significance in MMP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.102); Very rare (popmax 0.00668%, eas).

How common is MMP14 p.Arg160His (c.479G>A) in the general population?

MMP14 p.Arg160His (c.479G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about MMP14 p.Arg160His (c.479G>A)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

MMP14 p.Arg160His

c.479G>A · rs769434703 · VCV1512738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.155	moderately benign-leaning
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP -1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,799 bp · p 5.5e-10 · regional, not allelic
Overall
CADD	32.0	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 0.00668% East Asian · 3/44,884 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00328% 53/1,613,906 alleles · very rare exomes 52/1,461,726 · genomes 1/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,961
Admixed American	0.005%	19,995
African / African-American	0.004%	24,976
European (non-Finnish)	0.00339%	29,499
South Asian	0.00329%	30,357
Finnishnot grpmax-eligible	0.00156%	63,988

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.Arg160His
Coding: c.479G>A
MANE Select: NM_004995
dbSNP: rs769434703
Type: single nucleotide variant
Location: chr14:22842508 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 12 PDB
Residue 160: a β-strand

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

Similar variants

MMP14 p.Arg160= 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-arg160his (accessed [today's date]).

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