Is NBN p.Ala734= (c.2202A>G) pathogenic?

NBN p.Ala734= (c.2202A>G) is classified Benign/Likely benign in NBN (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-03-01). Ultra-rare (popmax 0.0181%, nfe); Associated with acute lymphoblastic leukemia.

What condition is associated with NBN p.Ala734= (c.2202A>G)?

NBN p.Ala734= (c.2202A>G) is associated with acute lymphoblastic leukemia, Nijmegen breakage syndrome, hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Ala734= (c.2202A>G) in the general population?

NBN p.Ala734= (c.2202A>G) is ultra-rare (popmax 0.0181%, nfe) (gnomAD).

NBN p.Ala734=

c.2202A>G · rs200452212 · VCV136042

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, nfe)

Conditions

acute lymphoblastic leukemia

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 -1.4	GERP -0.9, phastCons 0.001
Overall
CADD	7.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% European (non-Finnish) · 214/1,179,338 alleles

Filtering AF 0.0161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0153%

Overall 0.0145% 234/1,612,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0181%	5,511
Middle Eastern	0.0165%	6,046
Finnishnot grpmax-eligible	0.011%	9,096
Admixed American	0.01%	9,991
Remaining individualsnot grpmax-eligible	0.00641%	15,611
African / African-American	0.00267%	37,457

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.Ala734=
Coding: c.2202A>G
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs200452212
Type: single nucleotide variant
Location: chr8:89937058 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB

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

Disease context

acute lymphoblastic leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Nijmegen breakage syndrome hereditary neoplastic syndrome aplastic anemia

Similar variants

NBN p.Ala734Gly Uncertain significance ★★ ⚠ same residue
NBN p.Ala734Val Uncertain significance ★★ ⚠ same residue
NBN p.Ala734Thr 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
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-ala734 (accessed [today's date]).

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