Is NLRP3 p.Cys6= (c.18C>T) pathogenic?

NLRP3 p.Cys6= (c.18C>T) is classified Likely benign in NLRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). Very rare (popmax 0.00134%, afr); Associated with cryopyrin-associated periodic syndrome.

What condition is associated with NLRP3 p.Cys6= (c.18C>T)?

NLRP3 p.Cys6= (c.18C>T) is associated with cryopyrin-associated periodic syndrome (ClinVar).

How common is NLRP3 p.Cys6= (c.18C>T) in the general population?

NLRP3 p.Cys6= (c.18C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

NLRP3 p.Cys6=

c.18C>T · rs1304980958 · VCV862271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 0.96	GERP 0.86, phastCons 1
Overall
CADD	9.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,898 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00062% 10/1,613,866 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,898
European (non-Finnish)	0.000763%	131,115

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.Cys6=
Coding: c.18C>T
MANE Select: NM_001243133
dbSNP: rs1304980958
Type: single nucleotide variant
Location: chr1:247418818 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 6: the pyrin domain; an α-helix

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-cys6 (accessed [today's date]).

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