NBN p.Ser438=
c.1314T>C · rs1057521491 · VCV382946
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000339%, 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 2.4 | GERP 0.49, phastCons 0.007 |
| Overall | ||
| CADD | 3.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,179,776 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,613,796 alleles · very rare
exomes 4/1,461,610 · genomes 0/152,186 · 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
- NBN
- Protein
- p.Ser438=
- Coding
- c.1314T>C
- MANE Select
- NM_002485
- dbSNP
- rs1057521491
- Type
- single nucleotide variant
- Location
- chr8:89955366 (GRCh38)
- Structure
- AlphaFold pLDDT 75.83 · 5 PDB
Similar variants
- NBN p.Ser438Asn Uncertain significance ★★ ⚠ same residue
- NBN p.Ser438Ile Uncertain significance ★★ ⚠ same residue
- NBN p.Ser438Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- NBN p.Ser438fs 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
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-ser438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown