Is NBN p.Val157= (c.471T>G) pathogenic?

NBN p.Val157= (c.471T>G) is classified Likely benign in NBN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-07-04). Absent from gnomAD v4.1; Associated with Nijmegen breakage syndrome.

What condition is associated with NBN p.Val157= (c.471T>G)?

NBN p.Val157= (c.471T>G) is associated with Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Val157= (c.471T>G) in the general population?

NBN p.Val157= (c.471T>G) is absent from gnomAD v4.1 (gnomAD).

NBN p.Val157=

c.471T>G · rs864622275 · VCV1099114

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Nijmegen breakage syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor loss, 15 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.5	GERP -2.5, phastCons 1
Overall
CADD	7.017	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.Val157=
Coding: c.471T>G
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs864622275
Type: single nucleotide variant
Location: chr8:89980743 (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

Similar variants

NBN p.Val157Ile Uncertain significance ★★ ⚠ same residue
NBN p.Val157fs Pathogenic ★★ same residue
ARTN p.Ala157Ser 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
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-val157 (accessed [today's date]).

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