Is NBN p.Glu575Ter (c.1723G>T) pathogenic?

NBN p.Glu575Ter (c.1723G>T) is classified Pathogenic/Likely pathogenic in NBN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-04-12). Very rare (popmax 0.000254%, nfe); Associated with Nijmegen breakage syndrome.

What condition is associated with NBN p.Glu575Ter (c.1723G>T)?

NBN p.Glu575Ter (c.1723G>T) is associated with Nijmegen breakage syndrome, acute lymphoblastic leukemia, hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Glu575Ter (c.1723G>T) in the general population?

NBN p.Glu575Ter (c.1723G>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

NBN p.Glu575Ter

c.1723G>T · rs786201745 · VCV184862

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Nijmegen breakage syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 0.038
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,768 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,382 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.Glu575Ter
Coding: c.1723G>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs786201745
Type: single nucleotide variant
Location: chr8:89953366 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB

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: acute lymphoblastic leukemia hereditary neoplastic syndrome aplastic anemia

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-glu575ter (accessed [today's date]).

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