Is MMP8 p.Phe303Ser (c.908T>C) pathogenic?

MMP8 p.Phe303Ser (c.908T>C) is classified Uncertain significance in MMP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely pathogenic (0.7745); Absent from gnomAD v4.1.

How common is MMP8 p.Phe303Ser (c.908T>C) in the general population?

MMP8 p.Phe303Ser (c.908T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MMP8 p.Phe303Ser (c.908T>C)?

AlphaMissense predicts likely pathogenic (score 0.7745) — an in-silico prediction, not a clinical call.

MMP8 p.Phe303Ser

c.908T>C · rs2496375320 · VCV2330670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7745 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7745	likely pathogenic
REVEL	0.229	benign-leaning
SaProt	LLR -13.73	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 12 kb · p 4.9e-05 · regional, not allelic
Overall
CADD	27.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MMP8
Protein: p.Phe303Ser
Coding: c.908T>C
MANE Select: NM_002424
dbSNP: rs2496375320
Type: single nucleotide variant
Location: chr11:102715432 (GRCh38)
Gene constraint: LOEUF 1.464 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.56 · 25 PDB
Residue 303: a disulfide bond

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-phe303ser (accessed [today's date]).

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