Is FPR2 p.Cys296Trp (c.888C>G) pathogenic?

FPR2 p.Cys296Trp (c.888C>G) is classified Uncertain significance in FPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-06). AlphaMissense: likely pathogenic (0.9456); Ultra-rare (popmax 0.0353%, nfe).

How common is FPR2 p.Cys296Trp (c.888C>G) in the general population?

FPR2 p.Cys296Trp (c.888C>G) is ultra-rare (popmax 0.0353%, nfe) (gnomAD).

What do computational predictors say about FPR2 p.Cys296Trp (c.888C>G)?

AlphaMissense predicts likely pathogenic (score 0.9456) — an in-silico prediction, not a clinical call.

FPR2 p.Cys296Trp

c.888C>G · rs200897681 · VCV2368002

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9456 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0353%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9456	likely pathogenic · top 4% in FPR2
REVEL	0.571	indeterminate
SaProt	LLR -14.68	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP 0.93, phastCons 0.44
Regional constraint	o/e 0.85	unconstrained · MANE · 1,052 bp · p 0.0023 · regional, not allelic
Overall
CADD	23.8	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 0.0353% European (non-Finnish) · 416/1,180,054 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.0287% 463/1,614,104 alleles · ultra-rare exomes 442/1,461,892 · genomes 21/152,212 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.04%	2,500
European (non-Finnish)grpmax	0.0353%	2,837
Middle Eastern	0.0164%	6,084
Finnishnot grpmax-eligible	0.0141%	7,116
South Asian	0.00659%	15,182
Admixed American	0.005%	20,000
African / African-American	0.004%	24,976

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys296Trp
Coding: c.888C>G
MANE Select: NM_001005738
dbSNP: rs200897681
Type: single nucleotide variant
Location: chr19:51769546 (GRCh38)
Gene constraint: LOEUF 1.667 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 13 PDB
Residue 296: 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.Cys98Arg 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-cys296trp (accessed [today's date]).

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