NLRP3 p.Ser747=
c.2241T>C · rs199535084 · VCV1105985
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00593%, nfe)
Conditions
2
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 -0.87 | GERP -3.7, phastCons 0.019 |
| Overall | ||
| CADD | 1.222 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00593%
European (non-Finnish) · 70/1,179,994 alleles
Filtering AF
0.00478%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00439%
Overall
0.00434%
70/1,614,000 alleles · very rare
exomes 67/1,461,852 · genomes 3/152,148 · joint denominator
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.Ser747=
- Coding
- c.2241T>C
- MANE Select
- NM_001243133
- dbSNP
- rs199535084
- Type
- single nucleotide variant
- Location
- chr1:247429675 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.16 · 27 PDB
- Residue 747
- a β-strand
Similar variants
- NLRP3 p.Ser747Arg 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-ser747 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown