Is NBN p.Arg714Ter (c.2140C>T) pathogenic?

NBN p.Arg714Ter (c.2140C>T) is classified Pathogenic/Likely pathogenic in NBN (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-01-22). Very rare (popmax 0.00549%, sas); Associated with Nijmegen breakage syndrome.

What condition is associated with NBN p.Arg714Ter (c.2140C>T)?

NBN p.Arg714Ter (c.2140C>T) is associated with Nijmegen breakage syndrome, acute lymphoblastic leukemia, hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Arg714Ter (c.2140C>T) in the general population?

NBN p.Arg714Ter (c.2140C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

NBN p.Arg714Ter

c.2140C>T · rs730881864 · VCV182737

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 3.6	GERP 0.97, phastCons 1
Overall
CADD	37.0	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 0.00549% South Asian · 5/91,068 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00211% 34/1,613,316 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,214
Remaining individualsnot grpmax-eligible	0.0032%	31,231
European (non-Finnish)	0.00229%	43,689

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.Arg714Ter
Coding: c.2140C>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs730881864
Type: single nucleotide variant
Location: chr8:89943297 (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 p.Arg714Gln Uncertain significance ★★ ⚠ same residue
NBN p.Arg714= Conflicting classifications of pathogenicity ★ same residue
NBN p.Arg714Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
NBN p.Arg714Pro Uncertain significance ★ ⚠ same residue
NBN p.Arg714fs Likely pathogenic ★ 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

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-arg714ter (accessed [today's date]).

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