NLRP3 p.Ser588=
c.1764C>T · VCV3608781
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00534%, afr)
Conditions
1
cryopyrin-associated periodic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -3.7 |
| Overall | ||
| CADD | 1.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00534%
African / African-American · 4/74,908 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00263%
4/152,084 alleles · very rare
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
- NLRP3
- Protein
- p.Ser588=
- Coding
- c.1764C>T
- MANE Select
- NM_001243133
- Type
- single nucleotide variant
- Location
- chr1:247425213 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.16 · 27 PDB
Similar variants
- NLRP3 p.Ala352Thr Likely pathogenic ★★ same condition
- NLRP3 p.Ala352Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- NLRP3 p.Ala439Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- NLRP3 p.Ala439Val Pathogenic/Likely pathogenic ★★ same condition
- NLRP3 p.Arg260Ter Pathogenic ★★ same condition
- NLRP3 p.Asp303Asn Pathogenic ★★ ⚠ same condition
- NLRP3 p.Glu304Lys Pathogenic ★★ same condition
- NLRP3 p.Glu311Lys Pathogenic ★★ ⚠ 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/nlrp3-p-ser588 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown