NLRP3 p.Glu89=
c.267G>A · rs1662258352 · VCV2799780
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
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 0.63 | GERP -0.54, phastCons 1 |
| Overall | ||
| CADD | 3.362 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,970 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,610,676 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.Glu89=
- Coding
- c.267G>A
- MANE Select
- NM_001243133
- dbSNP
- rs1662258352
- Type
- single nucleotide variant
- Location
- chr1:247419067 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.16 · 27 PDB
- Residue 89
- the pyrin domain; an α-helix; a disulfide bond
Similar variants
- AVP p.Gln89Glu Uncertain significance ★ ⚠ same residue
- 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
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-glu89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown