Is FPR1 p.Val69Met (c.205G>A) pathogenic?

FPR1 p.Val69Met (c.205G>A) is classified Uncertain significance in FPR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1568); Ultra-rare (popmax 0.02%, amr); Associated with gingival disorder.

What condition is associated with FPR1 p.Val69Met (c.205G>A)?

FPR1 p.Val69Met (c.205G>A) is associated with gingival disorder (ClinVar).

How common is FPR1 p.Val69Met (c.205G>A) in the general population?

FPR1 p.Val69Met (c.205G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about FPR1 p.Val69Met (c.205G>A)?

AlphaMissense predicts likely benign (score 0.1568) — an in-silico prediction, not a clinical call.

FPR1 p.Val69Met

c.205G>A · rs199534146 · VCV660114

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1568 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

gingival disorder

Computational evidence

Protein change
AlphaMissense	0.1568	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -9.88	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 -9.3	GERP -3.7
Regional constraint	o/e 0.90	unconstrained · MANE · 1,049 bp · p 0.031 · regional, not allelic
Overall
CADD	0.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.02% Admixed American · 12/60,024 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00564% 91/1,614,140 alleles · ultra-rare exomes 85/1,461,890 · genomes 6/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,002
Remaining individualsnot grpmax-eligible	0.0112%	8,930
European (non-Finnish)	0.00568%	17,612
African / African-American	0.004%	25,003
South Asian	0.0022%	45,536

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.Val69Met
Coding: c.205G>A
MANE Select: NM_002029
dbSNP: rs199534146
Type: single nucleotide variant
Location: chr19:51746790 (GRCh38)
Gene constraint: LOEUF 1.921 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 84.17 · 5 PDB
Residue 69: 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-val69met (accessed [today's date]).

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