Is NBN p.His701= (c.2103C>T) pathogenic?

NBN p.His701= (c.2103C>T) is classified Likely benign in NBN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-22). Very rare (popmax 8.5e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.His701= (c.2103C>T)?

NBN p.His701= (c.2103C>T) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.His701= (c.2103C>T) in the general population?

NBN p.His701= (c.2103C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

NBN p.His701=

c.2103C>T · rs753991062 · VCV461539

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -0.93, phastCons 0.87
Overall
CADD	6.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,176 alleles

Overall 6.86e-05% 1/1,457,546 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.His701=
Coding: c.2103C>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs753991062
Type: single nucleotide variant
Location: chr8:89943334 (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.His701Tyr Uncertain significance ★★ ⚠ same residue
NBN p.His701Leu Uncertain significance ★ ⚠ same residue
NBN p.His701Pro Uncertain significance ★ ⚠ same residue
NBN p.His701fs Uncertain significance ★ same residue
NBN p.His701Arg Uncertain significance ★ ⚠ 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-his701 (accessed [today's date]).

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