Is NBN p.Arg89Ter (c.265C>T) pathogenic?

NBN p.Arg89Ter (c.265C>T) is classified Pathogenic/Likely pathogenic in NBN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-12). Very rare (popmax 0.0022%, sas); Associated with NBN-related disorder.

What condition is associated with NBN p.Arg89Ter (c.265C>T)?

NBN p.Arg89Ter (c.265C>T) is associated with NBN-related disorder, gastric cancer, acute lymphoblastic leukemia (ClinVar).

How common is NBN p.Arg89Ter (c.265C>T) in the general population?

NBN p.Arg89Ter (c.265C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

NBN p.Arg89Ter

c.265C>T · rs1057516320 · VCV370213

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

NBN-related disorder

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 1.7	GERP -0.84, phastCons 0.004
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 0.0022% South Asian · 2/91,076 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000274% 4/1,461,754 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,538
European (non-Finnish)	0.000169%	589,974

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.Arg89Ter
Coding: c.265C>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1057516320
Type: single nucleotide variant
Location: chr8:89981430 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 89: the 'disordered' region

Full NBN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NBN-related disorder

Also linked: gastric cancer acute lymphoblastic leukemia Nijmegen breakage syndrome hereditary neoplastic syndrome aplastic anemia

Similar variants

NBN p.Arg89= Likely benign ★★ same residue
NBN p.Arg89Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
NBN p.Arg89Gly Uncertain significance ★ ⚠ same residue
NBN p.Arg89Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
NBN p.Arg89Leu Uncertain significance ⚠ same residue
ARTN p.Ala89Thr Uncertain significance ★ ⚠ same residue
NBN c.1124+1G>C Likely pathogenic ★★ same condition
NBN c.1124+2T>G 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-arg89ter (accessed [today's date]).

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