Is MMP14 p.Ala4Thr (c.10G>A) pathogenic?

MMP14 p.Ala4Thr (c.10G>A) is classified Benign in MMP14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0952); Low-frequency (popmax 3.18%, afr).

How common is MMP14 p.Ala4Thr (c.10G>A) in the general population?

MMP14 p.Ala4Thr (c.10G>A) is low-frequency (popmax 3.18%, afr) (gnomAD).

What do computational predictors say about MMP14 p.Ala4Thr (c.10G>A)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

MMP14 p.Ala4Thr

c.10G>A · rs17882219 · VCV776819

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.18%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.48	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 2	GERP 0.003, phastCons 0.99
Regional constraint	o/e 0.92	unconstrained · MANE · 4,675 bp · p 0.59 · regional, not allelic
Overall
CADD	18.83	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 3.18% African / African-American · 2,371/74,552 alleles

Filtering AF 3.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.03%

Overall 0.169% 2,709/1,603,280 alleles · low-frequency exomes 1,382/1,451,212 · genomes 1,327/152,068 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.18%	31
Middle Eastern	0.233%	429
Admixed American	0.196%	510
Remaining individualsnot grpmax-eligible	0.195%	512
European (non-Finnish)	0.00724%	13,803
South Asian	0.00223%	44,934

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.Ala4Thr
Coding: c.10G>A
MANE Select: NM_004995
dbSNP: rs17882219
Type: single nucleotide variant
Location: chr14:22836827 (GRCh38)
Gene constraint: LOEUF 0.312 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.66 · 12 PDB
Residue 4: a UniProt-annotated variant site (in)

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

Similar variants

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
MMP14 p.Arg362Gln 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-ala4thr (accessed [today's date]).

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