Is NBN p.Lys160= (c.480A>G) pathogenic?

NBN p.Lys160= (c.480A>G) is classified Conflicting classifications of pathogenicity in NBN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-11-28). Very rare (popmax 0.0067%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Lys160= (c.480A>G)?

NBN p.Lys160= (c.480A>G) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Lys160= (c.480A>G) in the general population?

NBN p.Lys160= (c.480A>G) is very rare (popmax 0.0067%, eas) (gnomAD).

NBN p.Lys160=

c.480A>G · rs1554567842 · VCV481850

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0067%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.42	donor loss, 24 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.5	GERP -2.3, phastCons 1
Overall
CADD	14.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% East Asian · 3/44,774 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000206% 3/1,457,414 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.Lys160=
Coding: c.480A>G
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1554567842
Type: single nucleotide variant
Location: chr8:89980734 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 160: a disulfide bond; an α-helix

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 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
NBN c.172-2A>G Likely pathogenic ★★ same condition
NBN c.1845+1G>A Likely pathogenic ★★ same condition
NBN c.2070+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-lys160 (accessed [today's date]).

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