Is MMP14 p.Ala37Pro (c.109G>C) pathogenic?

MMP14 p.Ala37Pro (c.109G>C) is classified Likely benign in MMP14 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-24). AlphaMissense: likely pathogenic (0.6926); Rare (popmax 0.509%, afr).

How common is MMP14 p.Ala37Pro (c.109G>C) in the general population?

MMP14 p.Ala37Pro (c.109G>C) is rare (popmax 0.509%, afr) (gnomAD).

What do computational predictors say about MMP14 p.Ala37Pro (c.109G>C)?

AlphaMissense predicts likely pathogenic (score 0.6926) — an in-silico prediction, not a clinical call.

MMP14 p.Ala37Pro

c.109G>C · rs139288377 · VCV729027

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6926 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.509%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6926	likely pathogenic
REVEL	0.227	benign-leaning
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,675 bp · p 0.59 · 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 0.509% African / African-American · 382/75,022 alleles

Filtering AF 0.467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.45%

Overall 0.026% 420/1,613,478 alleles · rare exomes 178/1,461,208 · genomes 242/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.509%	196
Remaining individualsnot grpmax-eligible	0.0368%	2,716
Admixed American	0.0217%	4,616
South Asian	0.0011%	91,074
European (non-Finnish)	8.47e-05%	1,179,974

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.Ala37Pro
Coding: c.109G>C
MANE Select: NM_004995
dbSNP: rs139288377
Type: single nucleotide variant
Location: chr14:22841491 (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 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-ala37pro (accessed [today's date]).

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