Is FPR2 p.Pro213Leu (c.638C>T) pathogenic?

FPR2 p.Pro213Leu (c.638C>T) is classified Uncertain significance in FPR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely pathogenic (0.7838); Ultra-rare (popmax 0.0373%, afr).

How common is FPR2 p.Pro213Leu (c.638C>T) in the general population?

FPR2 p.Pro213Leu (c.638C>T) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

What do computational predictors say about FPR2 p.Pro213Leu (c.638C>T)?

AlphaMissense predicts likely pathogenic (score 0.7838) — an in-silico prediction, not a clinical call.

FPR2 p.Pro213Leu

c.638C>T · rs141356657 · VCV2492428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7838 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7838	likely pathogenic
REVEL	0.386	indeterminate
SaProt	LLR -12.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.9, phastCons 0.96
Regional constraint	o/e 0.85	unconstrained · MANE · 1,052 bp · p 0.0023 · regional, not allelic
Overall
CADD	23.0	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 0.0373% African / African-American · 28/75,032 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00223% 36/1,614,168 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,680
Admixed American	0.005%	20,007
East Asian	0.00223%	44,872
South Asian	0.0022%	45,544
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,030

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.Pro213Leu
Coding: c.638C>T
MANE Select: NM_001005738
dbSNP: rs141356657
Type: single nucleotide variant
Location: chr19:51769296 (GRCh38)
Gene constraint: LOEUF 1.667 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 84.87 · 13 PDB
Residue 213: 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-pro213leu (accessed [today's date]).

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