Is MMP14 p.Asp320Asn (c.958G>A) pathogenic?

MMP14 p.Asp320Asn (c.958G>A) is classified Uncertain significance in MMP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-05). AlphaMissense: likely benign (0.143); Ultra-rare (popmax 0.0869%, amr); Associated with Inborn genetic diseases.

What condition is associated with MMP14 p.Asp320Asn (c.958G>A)?

MMP14 p.Asp320Asn (c.958G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MMP14 p.Asp320Asn (c.958G>A) in the general population?

MMP14 p.Asp320Asn (c.958G>A) is ultra-rare (popmax 0.0869%, amr) (gnomAD).

What do computational predictors say about MMP14 p.Asp320Asn (c.958G>A)?

AlphaMissense predicts likely benign (score 0.143) — an in-silico prediction, not a clinical call.

MMP14 p.Asp320Asn

c.958G>A · rs143934919 · VCV1425469

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.143 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.143	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -6.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,683 bp · p 0.003 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.0869% Admixed American · 52/59,822 alleles

Filtering AF 0.068% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.00446% 72/1,613,664 alleles · ultra-rare exomes 29/1,461,422 · genomes 43/152,242 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0869%	1,150
Remaining individualsnot grpmax-eligible	0.0272%	3,675
African / African-American	0.004%	24,991

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.Asp320Asn
Coding: c.958G>A
MANE Select: NM_004995
dbSNP: rs143934919
Type: single nucleotide variant
Location: chr14:22843817 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 12 PDB
Residue 320: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MMP14 p.Asp320= Likely benign ★ same residue
MMP14 p.Ala165Asp Uncertain significance ★★ ⚠ same condition
MMP14 p.Ala366Val Uncertain significance ★★ ⚠ same condition
MMP14 p.Ala539Thr Uncertain significance ★★ ⚠ same condition
MMP14 p.Ala539Val Uncertain significance ★★ ⚠ same condition
MMP14 p.Arg168Cys Uncertain significance ★★ ⚠ same condition
MMP14 p.Arg343Trp Uncertain significance ★★ ⚠ same condition
MMP14 p.Arg362Gln Uncertain significance ★★ ⚠ same condition

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-asp320asn (accessed [today's date]).

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