NOD2 p.Pro53=
c.159T>C · rs1404416626 · VCV1973669
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
Regional enteritis
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 -1 | GERP -4.5, phastCons 0.001 |
| Overall | ||
| CADD | 7.013 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,008 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,614,124 alleles · very rare
exomes 3/1,461,872 · genomes 0/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,008 |
| European (non-Finnish) | 0.000169% | 590,009 |
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
- NOD2
- Protein
- p.Pro53=
- Coding
- c.159T>C
- MANE Select
- NM_001370466
- dbSNP
- rs1404416626
- Type
- single nucleotide variant
- Location
- chr16:50699654 (GRCh38)
- Gene constraint
- LOEUF 1.033 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.76
- Residue 53
- the card 1 domain
Similar variants
- NOD2 p.Pro53Ala Uncertain significance ★ ⚠ same residue
- NOD2 p.Pro53Thr Uncertain significance ★ ⚠ same residue
- NOD2 p.Arg307Gln Pathogenic ★★ ⚠ same condition
- NOD2 p.Arg307Trp Pathogenic ★★ ⚠ same condition
- NOD2 p.Arg560Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- NOD2 p.Met486Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
- NOD2 c.2550-2A>G Uncertain significance ★★ same condition
- NOD2 c.2717+2T>A 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/nod2-p-pro53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown