Is NLRC4 p.Asp83= (c.249C>T) pathogenic?

NLRC4 p.Asp83= (c.249C>T) is classified Conflicting classifications of pathogenicity in NLRC4 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-28). Very rare (popmax 0.00621%, nfe); Associated with autoinflammatory syndrome.

How common is NLRC4 p.Asp83= (c.249C>T) in the general population?

NLRC4 p.Asp83= (c.249C>T) is very rare (popmax 0.00621%, nfe) (gnomAD).

NLRC4 p.Asp83=

Q: What condition is associated with NLRC4 p.Asp83= (c.249C>T)?

NLRC4 p.Asp83= (c.249C>T) is associated with autoinflammatory syndrome, periodic fever-infantile enterocolitis-autoinflammatory syndrome, familial cold autoinflammatory syndrome 4 (ClinVar).

c.249C>T · rs117094017 · VCV1116165

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00621%, 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 2.3	GERP -0.63, phastCons 1
Overall
CADD	4.833	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00621% European (non-Finnish) · 73/1,174,632 alleles

Filtering AF 0.00505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00465%

Overall 0.00466% 75/1,608,174 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00621%	16,091
East Asian	0.00223%	44,856
Remaining individualsnot grpmax-eligible	0.00161%	62,278

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: NLRC4
Protein: p.Asp83=
Coding: c.249C>T
MANE Select: NM_001199138
dbSNP: rs117094017
Type: single nucleotide variant
Location: chr2:32252432 (GRCh38)
Gene constraint: LOEUF 0.948 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.18 · 6 PDB
Residue 83: the card domain; an α-helix

Full NLRC4 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: periodic fever-infantile enterocolitis-autoinflammatory syndrome familial cold autoinflammatory syndrome 4

Similar variants

NLRC4 p.Ser445Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
NLRC4 p.Val341Ala Pathogenic ★★ ⚠ same condition
NLRC4 c.2351-8T>G Uncertain significance ★★ same condition
NLRC4 p.Ala1018Thr Uncertain significance ★★ ⚠ same condition
NLRC4 p.Ala193Pro Uncertain significance ★★ ⚠ same condition
NLRC4 p.Ala234Val Uncertain significance ★★ ⚠ same condition
NLRC4 p.Ala318Pro Uncertain significance ★★ ⚠ same condition
NLRC4 p.Ala982Glu Uncertain significance ★★ ⚠ 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/nlrc4-p-asp83 (accessed [today's date]).

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