NBN p.His149=
c.447C>T · rs868089138 · VCV701530
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Conditions
2
Nijmegen breakage 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 -0.041 | GERP -0.94, phastCons 0.17 |
| Overall | ||
| CADD | 5.731 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,504 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000205%
3/1,461,104 alleles · very rare
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
- NBN
- Protein
- p.His149=
- Coding
- c.447C>T
- MANE Select
- NM_057091 · reported on NM_002485
- dbSNP
- rs868089138
- Type
- single nucleotide variant
- Location
- chr8:89980767 (GRCh38)
- Structure
- AlphaFold pLDDT 75.83 · 5 PDB
- Residue 149
- a β-strand; a disulfide bond
Similar variants
- NBN p.His149Gln Uncertain significance ★★ ⚠ same residue
- NBN p.His149Tyr Uncertain significance ★★ ⚠ same residue
- NBN p.His149fs Pathogenic/Likely pathogenic ★★ same residue
- NBN c.1124+1G>C Likely pathogenic ★★ same condition
- NBN c.1124+2T>G Likely pathogenic ★★ same condition
- NBN c.1397+2T>A Likely pathogenic ★★ same condition
- NBN c.171+1G>A Likely pathogenic ★★ same condition
- NBN c.172-1G>T Likely 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/nbn-p-his149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown