Is NLRP3 p.Pro340= (c.1020C>T) pathogenic?

NLRP3 p.Pro340= (c.1020C>T) is classified Benign/Likely benign in NLRP3 (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-06-01). Rare (popmax 0.72%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with NLRP3 p.Pro340= (c.1020C>T)?

NLRP3 p.Pro340= (c.1020C>T) is associated with autoinflammatory syndrome, familial cold autoinflammatory syndrome 1, Muckle-Wells syndrome (ClinVar).

How common is NLRP3 p.Pro340= (c.1020C>T) in the general population?

NLRP3 p.Pro340= (c.1020C>T) is rare (popmax 0.72%, nfe) (gnomAD).

NLRP3 p.Pro340=

c.1020C>T · rs41311573 · VCV218548

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

rare (popmax 0.72%, nfe)

Conditions

autoinflammatory 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 -11	GERP -3.7
Overall
CADD	1.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.72% European (non-Finnish) · 8,501/1,180,036 alleles

Filtering AF 0.708% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.702%

Overall 0.628% 10,144/1,614,172 alleles · rare exomes 9,341/1,461,858 · genomes 803/152,314 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.72%	139
Admixed American	0.7%	143
Finnishnot grpmax-eligible	0.628%	159
Remaining individualsnot grpmax-eligible	0.624%	160
Amishnot grpmax-eligible	0.548%	182
Middle Eastern	0.413%	242
Ashkenazi Jewishnot grpmax-eligible	0.355%	282
East Asian	0.16%	623
South Asian	0.138%	723
African / African-American	0.131%	766

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.Pro340=
Coding: c.1020C>T
MANE Select: NM_001243133
dbSNP: rs41311573
Type: single nucleotide variant
Location: chr1:247424469 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.16 · 27 PDB
Residue 340: a β-strand; the nacht domain

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

Disease context

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial cold autoinflammatory syndrome 1 Muckle-Wells syndrome CINCA syndrome cryopyrin-associated periodic syndrome

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-pro340 (accessed [today's date]).

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