Is FPR3 p.Cys124Ser (c.370T>A) pathogenic?

FPR3 p.Cys124Ser (c.370T>A) is classified Uncertain significance in FPR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-21). AlphaMissense: ambiguous (0.4747); Very rare (popmax 0.00133%, afr).

How common is FPR3 p.Cys124Ser (c.370T>A) in the general population?

FPR3 p.Cys124Ser (c.370T>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about FPR3 p.Cys124Ser (c.370T>A)?

AlphaMissense predicts ambiguous (score 0.4747) — an in-silico prediction, not a clinical call.

FPR3 p.Cys124Ser

c.370T>A · rs1452241960 · VCV3096668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4747 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4747	ambiguous
REVEL	0.249	benign-leaning
SaProt	LLR -11.63	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 0.69, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 1,058 bp · p 3.9e-06 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,940 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,926 alleles · very rare exomes 1/1,461,692 · genomes 3/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,940
European (non-Finnish)	0.000254%	393,317

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: FPR3
Protein: p.Cys124Ser
Coding: c.370T>A
MANE Select: NM_002030
dbSNP: rs1452241960
Type: single nucleotide variant
Location: chr19:51824118 (GRCh38)
Gene constraint: LOEUF 1.906 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 83.62

Full FPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FPR3 p.Ala198Gly Uncertain significance ★ ⚠ same type
FPR3 p.Ala244Val Uncertain significance ★ ⚠ same type
FPR3 p.Ala86Thr Uncertain significance ★ ⚠ same type
FPR3 p.Arg123His Uncertain significance ★ ⚠ same type
FPR3 p.Arg241Cys Uncertain significance ★ ⚠ same type
FPR3 p.Arg57His Uncertain significance ★ ⚠ same type
FPR3 p.Asn274Tyr Uncertain significance ★ ⚠ same type
FPR3 p.Glu258Lys 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/fpr3-p-cys124ser (accessed [today's date]).

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