Is MMP8 p.Pro44Leu (c.131C>T) pathogenic?

MMP8 p.Pro44Leu (c.131C>T) is classified Uncertain significance in MMP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.1739); Very rare (popmax 0.00223%, eas).

How common is MMP8 p.Pro44Leu (c.131C>T) in the general population?

MMP8 p.Pro44Leu (c.131C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MMP8 p.Pro44Leu (c.131C>T)?

AlphaMissense predicts likely benign (score 0.1739) — an in-silico prediction, not a clinical call.

MMP8 p.Pro44Leu

c.131C>T · rs1305929828 · VCV3168730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1739 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1739	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -10.34	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 4.8	GERP -1.4, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 12 kb · p 4.9e-05 · regional, not allelic
Overall
CADD	14.07	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 0.00223% East Asian · 1/44,886 alleles

Overall 0.000137% 2/1,461,464 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
European (non-Finnish)	8.48e-05%	1,179,743

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: MMP8
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_002424
dbSNP: rs1305929828
Type: single nucleotide variant
Location: chr11:102722645 (GRCh38)
Gene constraint: LOEUF 1.464 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.56 · 25 PDB

Full MMP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MMP8 c.785-4C>T Likely benign ★★ same type
MMP8 p.Arg118Gln Benign ★★ same type
MMP8 p.Asn463Asp Benign ★★ same type
MMP8 p.Gln450Ter Likely benign ★★ same type
MMP8 p.Glu81Lys Likely benign ★★ ⚠ same type
MMP8 p.Lys87Glu Benign ★★ ⚠ same type
MMP8 p.Val60Ile Benign ★★ same type
MMP8 p.Ala127Ser 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/mmp8-p-pro44leu (accessed [today's date]).

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