Is NBN p.Leu48= (c.144A>G) pathogenic?

NBN p.Leu48= (c.144A>G) is classified Likely benign in NBN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Leu48= (c.144A>G)?

NBN p.Leu48= (c.144A>G) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Leu48= (c.144A>G) in the general population?

NBN p.Leu48= (c.144A>G) is absent from gnomAD v4.1 (gnomAD).

NBN p.Leu48=

c.144A>G · rs1563584056 · VCV754554

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.5	GERP 0.7, phastCons 1
Overall
CADD	12.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NBN
Protein: p.Leu48=
Coding: c.144A>G
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1563584056
Type: single nucleotide variant
Location: chr8:89982749 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 48: the 'disordered' region

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.Leu48Ter Pathogenic ★ same residue
NBN p.Leu48Ser Uncertain significance ★ ⚠ same residue
NBN p.Leu48Val Uncertain significance ★ ⚠ same residue
NBN p.Leu48fs 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

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-leu48 (accessed [today's date]).

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