NLRP3 p.Phe255=
c.765C>T · rs753671377 · VCV2879505
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00892%, eas)
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 0.1 | GERP -1.4, phastCons 0.94 |
| Overall | ||
| CADD | 4.924 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00892%
East Asian · 4/44,858 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000274%
4/1,461,858 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.Phe255=
- Coding
- c.765C>T
- MANE Select
- NM_001243133
- dbSNP
- rs753671377
- Type
- single nucleotide variant
- Location
- chr1:247424214 (GRCh38)
- Gene constraint
- LOEUF 0.639 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.16 · 27 PDB
- Residue 255
- a β-strand; the nacht domain
Similar variants
- NLRP3 p.Phe255fs 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-phe255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown