Is FPR2 p.Val266Ile (c.796G>A) pathogenic?

FPR2 p.Val266Ile (c.796G>A) is classified Uncertain significance in FPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0762); Ultra-rare (popmax 0.0167%, amr).

How common is FPR2 p.Val266Ile (c.796G>A) in the general population?

FPR2 p.Val266Ile (c.796G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about FPR2 p.Val266Ile (c.796G>A)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

FPR2 p.Val266Ile

c.796G>A · rs554489638 · VCV3096662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.47	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 -4	GERP -3.4
Regional constraint	o/e 0.85	unconstrained · MANE · 1,052 bp · p 0.0023 · regional, not allelic
Overall
CADD	0.616	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 0.0167% Admixed American · 10/60,016 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00533% 86/1,614,138 alleles · ultra-rare exomes 70/1,461,886 · genomes 16/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,002
Finnishnot grpmax-eligible	0.00625%	16,009
European (non-Finnish)	0.00542%	18,438
African / African-American	0.004%	25,009
South Asian	0.00329%	30,359
East Asian	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: FPR2
Protein: p.Val266Ile
Coding: c.796G>A
MANE Select: NM_001005738
dbSNP: rs554489638
Type: single nucleotide variant
Location: chr19:51769454 (GRCh38)
Gene constraint: LOEUF 1.667 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 13 PDB
Residue 266: an α-helix

Full FPR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FPR2 p.Phe74Leu Benign/Likely benign ★★ ⚠ same type
FPR2 c.-15+1402C>T Uncertain significance ★ same type
FPR2 p.Ala245Val Uncertain significance ★ ⚠ same type
FPR2 p.Ala248Ser Uncertain significance ★ ⚠ same type
FPR2 p.Arg137Cys Uncertain significance ★ same type
FPR2 p.Arg57Cys Uncertain significance ★ ⚠ same type
FPR2 p.Arg57His Uncertain significance ★ ⚠ same type
FPR2 p.Cys296Trp 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/fpr2-p-val266ile (accessed [today's date]).

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