Is NLRP3 p.Leu206= (c.616C>T) pathogenic?

NLRP3 p.Leu206= (c.616C>T) is classified Likely benign in NLRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). Absent from gnomAD v4.1; Associated with cryopyrin-associated periodic syndrome.

What condition is associated with NLRP3 p.Leu206= (c.616C>T)?

NLRP3 p.Leu206= (c.616C>T) is associated with cryopyrin-associated periodic syndrome (ClinVar).

How common is NLRP3 p.Leu206= (c.616C>T) in the general population?

NLRP3 p.Leu206= (c.616C>T) is absent from gnomAD v4.1 (gnomAD).

NLRP3 p.Leu206=

c.616C>T · rs2527257054 · VCV2004129

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 2.1	GERP 0.74, phastCons 0.97
Overall
CADD	4.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NLRP3
Protein: p.Leu206=
Coding: c.616C>T
MANE Select: NM_001243133
dbSNP: rs2527257054
Type: single nucleotide variant
Location: chr1:247424065 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 206: an α-helix; the fisna domain

Full NLRP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cryopyrin-associated periodic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu206 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown