Is NBN p.Asn142= (c.426T>C) pathogenic?

NBN p.Asn142= (c.426T>C) is classified Benign/Likely benign in NBN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-21). Very rare (popmax 0.00966%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with NBN p.Asn142= (c.426T>C)?

NBN p.Asn142= (c.426T>C) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Asn142= (c.426T>C) in the general population?

NBN p.Asn142= (c.426T>C) is very rare (popmax 0.00966%, nfe) (gnomAD).

NBN p.Asn142=

c.426T>C · rs143070291 · VCV184528

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00966%, 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 -0.25	GERP -3.4
Overall
CADD	9.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00966% European (non-Finnish) · 114/1,179,686 alleles

Filtering AF 0.00818% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00738% 119/1,613,488 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00966%	10,348
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,452
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Asn142=
Coding: c.426T>C
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs143070291
Type: single nucleotide variant
Location: chr8:89980788 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 142: a disulfide bond

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.Asn142Asp Uncertain significance ★ ⚠ same residue
NBN p.Asn142His Uncertain significance ★ ⚠ same residue
NBN p.Asn142Ser Conflicting classifications of pathogenicity ★ ⚠ 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
NBN c.171+1G>A Likely pathogenic ★★ same condition
NBN c.172-1G>T 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-asn142 (accessed [today's date]).

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