NLRP3 p.Ser243=
c.729G>A · rs147198684 · VCV932659
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
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 -9.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.982 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,056 alleles
Filtering AF
0.00157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00134%
Overall
0.00204%
33/1,613,854 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,352 |
| African / African-American | 0.00267% | 37,432 |
| European (non-Finnish) | 0.00229% | 43,703 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
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.Ser243=
- Coding
- c.729G>A
- MANE Select
- NM_001243133
- dbSNP
- rs147198684
- Type
- single nucleotide variant
- Location
- chr1:247424178 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.16 · 27 PDB
- Residue 243
- an α-helix; the nacht domain
Similar variants
- NLRP3 p.Ser243Leu 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-ser243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown