NFKB1 p.Pro83=
c.249T>C · rs754219657 · VCV1617285
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000342%, nfe)
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 -0.28 | GERP -5, phastCons 0.39 |
| Overall | ||
| CADD | 8.565 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000342%
European (non-Finnish) · 4/1,170,408 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00025%
4/1,603,128 alleles · very rare
exomes 4/1,450,816 · genomes 0/152,312 · joint denominator
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
- NFKB1
- Protein
- p.Pro83=
- Coding
- c.249T>C
- MANE Select
- NM_003998
- dbSNP
- rs754219657
- Type
- single nucleotide variant
- Location
- chr4:102537947 (GRCh38)
- Gene constraint
- LOEUF 0.178 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.84 · 15 PDB
- Residue 83
- the rhd domain; a β-strand
Similar variants
- NFKB1 c.159+1G>A Pathogenic/Likely pathogenic ★★ same type
- NFKB1 c.1753-1G>C Likely pathogenic ★★ same type
- NFKB1 c.407+1G>A Pathogenic/Likely pathogenic ★★ same type
- NFKB1 c.407+2T>G Pathogenic/Likely pathogenic ★★ same type
- NFKB1 c.835+2T>C Likely pathogenic ★★ same type
- NFKB1 c.928-1G>A Likely pathogenic ★★ same type
- NFKB1 p.Arg157Ter Pathogenic ★★ same type
- NFKB1 p.Arg284Ter Pathogenic/Likely pathogenic ★★ same type
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/nfkb1-p-pro83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown