Is FPR1 p.Pro256Ser (c.766C>T) pathogenic?

FPR1 p.Pro256Ser (c.766C>T) is classified Uncertain significance in FPR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-29). AlphaMissense: likely pathogenic (0.8883); Very rare (popmax 8.47e-05%, nfe); Associated with gingival disorder.

What condition is associated with FPR1 p.Pro256Ser (c.766C>T)?

FPR1 p.Pro256Ser (c.766C>T) is associated with gingival disorder (ClinVar).

How common is FPR1 p.Pro256Ser (c.766C>T) in the general population?

FPR1 p.Pro256Ser (c.766C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about FPR1 p.Pro256Ser (c.766C>T)?

AlphaMissense predicts likely pathogenic (score 0.8883) — an in-silico prediction, not a clinical call.

FPR1 p.Pro256Ser

c.766C>T · VCV3684638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gingival disorder

Computational evidence

Protein change
AlphaMissense	0.8883	likely pathogenic · top 9% in FPR1
REVEL	0.782	moderately pathogenic-leaning
SaProt	LLR -12.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,049 bp · p 0.031 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 6.84e-05% 1/1,461,868 alleles · very rare

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: FPR1
Protein: p.Pro256Ser
Coding: c.766C>T
MANE Select: NM_002029
Type: single nucleotide variant
Location: chr19:51746229 (GRCh38)
Gene constraint: LOEUF 1.921 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 5 PDB
Residue 256: an α-helix

Full FPR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

gingival disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FPR1 p.Ala225Val Uncertain significance ★★ ⚠ same condition
FPR1 p.Ala315Thr Uncertain significance ★★ ⚠ same condition
FPR1 p.Ile146Val Uncertain significance ★★ ⚠ same condition
FPR1 p.Ile147Thr Uncertain significance ★★ ⚠ same condition
FPR1 p.Ile216Val Uncertain significance ★★ ⚠ same condition
FPR1 p.Ile228Phe Uncertain significance ★★ ⚠ same condition
FPR1 p.Met197Ile Uncertain significance ★★ ⚠ same condition
FPR1 p.Met275Thr 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/fpr1-p-pro256ser (accessed [today's date]).

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