Is NBN p.Leu5= (c.15G>A) pathogenic?

NBN p.Leu5= (c.15G>A) is classified Likely benign in NBN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-13). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Leu5= (c.15G>A)?

NBN p.Leu5= (c.15G>A) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Leu5= (c.15G>A) in the general population?

NBN p.Leu5= (c.15G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

NBN p.Leu5=

c.15G>A · rs1363180098 · VCV1663256

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic 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 -4.2	GERP -4
Overall
CADD	0.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,802 alleles

Overall 6.85e-05% 1/1,460,832 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.Leu5=
Coding: c.15G>A
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1363180098
Type: single nucleotide variant
Location: chr8:89984547 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB

Full NBN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Nijmegen breakage syndrome

Similar variants

NBN p.Leu5Arg Uncertain significance ★ ⚠ same residue
NBN p.Leu5Gln Uncertain significance ★ ⚠ same residue
NBN p.Leu5Pro Uncertain significance ★ ⚠ same residue
NBN p.Leu5fs Pathogenic/Likely pathogenic ★★ same residue
ARTN p.Leu5Val Uncertain significance ★ ⚠ 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

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-leu5 (accessed [today's date]).

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