Is NBN p.Ala8= (c.24G>T) pathogenic?

NBN p.Ala8= (c.24G>T) is classified Likely benign in NBN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). Very rare (popmax 0.00017%, nfe); Associated with Nijmegen breakage syndrome.

What condition is associated with NBN p.Ala8= (c.24G>T)?

NBN p.Ala8= (c.24G>T) is associated with Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Ala8= (c.24G>T) in the general population?

NBN p.Ala8= (c.24G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

NBN p.Ala8=

c.24G>T · rs779543740 · VCV1574877

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Nijmegen breakage 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 0.51	GERP -1.5, phastCons 0.034
Overall
CADD	6.327	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,784 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,824 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.Ala8=
Coding: c.24G>T
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs779543740
Type: single nucleotide variant
Location: chr8:89984538 (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

Similar variants

NBN p.Ala8Thr Uncertain significance ★★ ⚠ same residue
NBN p.Ala8Val Uncertain significance ★★ ⚠ same residue
NBN p.Ala8Gly Uncertain significance ★ ⚠ same residue
NBN p.Ala8Pro 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
NBN c.171+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-ala8 (accessed [today's date]).

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