Is NBN p.Gln451Pro (c.1352_1353delinsCC) pathogenic?

NBN p.Gln451Pro (c.13521353delinsCC) is classified Uncertain significance in NBN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-13). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Gln451Pro (c.1352_1353delinsCC)?

NBN p.Gln451Pro (c.1352_1353delinsCC) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Gln451Pro (c.1352_1353delinsCC) in the general population?

NBN p.Gln451Pro (c.1352_1353delinsCC) is absent from gnomAD (gnomAD).

NBN p.Gln451Pro

c.1352_1353delinsCC · rs1554559065 · VCV480062

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 0.79	GERP 0.91, phastCons 0.99

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NBN
Protein: p.Gln451Pro
Coding: c.1352_1353delinsCC
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1554559065
Type: Indel
Location: chr8:89955327 (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.Gln451Arg Uncertain significance ★★ ⚠ same residue
NBN p.Gln451Glu Uncertain significance ★★ ⚠ same residue
NBN p.Gln451= Likely benign ★★ same residue
NBN p.Gln451His Uncertain significance ★ ⚠ same residue
NBN c.585-1_585delinsC Likely pathogenic ★★ same condition
NBN p.Glu179fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Pro198fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Pro495fs Pathogenic/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-gln451pro (accessed [today's date]).

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