Is NBN p.Val157fs (c.468del) pathogenic?

NBN p.Val157fs (c.468del) is classified Pathogenic in NBN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-26). Ultra-rare (gnomAD MAF 1.68e-06); Associated with Nijmegen breakage syndrome.

What condition is associated with NBN p.Val157fs (c.468del)?

NBN p.Val157fs (c.468del) is associated with Nijmegen breakage syndrome, hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Val157fs (c.468del) in the general population?

NBN p.Val157fs (c.468del) is ultra-rare (gnomAD MAF 1.68e-06) (gnomAD).

NBN p.Val157fs

c.468del · rs1563578596 · VCV577077

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 1.68e-06)

Conditions

Nijmegen breakage syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

Global frequency 0.000168% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: NBN
Protein: p.Val157fs
Coding: c.468del
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1563578596
Type: Deletion
Location: chr8:89980746 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 157: a disulfide bond; an α-helix

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

Disease context

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

Also linked: hereditary neoplastic syndrome

Similar variants

NBN p.Val157Ile Uncertain significance ★★ ⚠ same residue
NBN p.Val157= Likely benign ★ same residue
NBN c.1397+1_1397+9del Likely pathogenic ★★ same condition
NBN c.1397+1del Pathogenic ★★ same condition
NBN c.163_171+3del Pathogenic/Likely pathogenic ★★ same condition
NBN c.2070+2del Likely pathogenic ★★ same condition
NBN c.2071del Pathogenic/Likely pathogenic ★★ same condition
NBN c.2226_2234+4del 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-val157fs (accessed [today's date]).

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