Is NLRP3 p.Val1028= (c.3084C>T) pathogenic?

NLRP3 p.Val1028= (c.3084C>T) is classified Likely benign in NLRP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Ultra-rare (popmax 0.0227%, afr); Associated with cryopyrin-associated periodic syndrome.

What condition is associated with NLRP3 p.Val1028= (c.3084C>T)?

NLRP3 p.Val1028= (c.3084C>T) is associated with cryopyrin-associated periodic syndrome (ClinVar).

How common is NLRP3 p.Val1028= (c.3084C>T) in the general population?

NLRP3 p.Val1028= (c.3084C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

NLRP3 p.Val1028=

c.3084C>T · rs201532680 · VCV747807

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

cryopyrin-associated periodic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -2.7	GERP -3.4
Overall
CADD	7.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,872 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00124% 20/1,612,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,404
Admixed American	0.00333%	30,000
European (non-Finnish)	8.48e-05%	1,178,688

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.Val1028=
Coding: c.3084C>T
MANE Select: NM_001243133
dbSNP: rs201532680
Type: single nucleotide variant
Location: chr1:247448483 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 1028: a β-strand

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.Val1028fs 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-val1028 (accessed [today's date]).

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