Is NBN p.Pro329= (c.987C>G) pathogenic?

NBN p.Pro329= (c.987C>G) is classified Likely benign in NBN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). Ultra-rare (popmax 0.0165%, mid); Associated with Nijmegen breakage syndrome.

What condition is associated with NBN p.Pro329= (c.987C>G)?

NBN p.Pro329= (c.987C>G) is associated with Nijmegen breakage syndrome (ClinVar).

How common is NBN p.Pro329= (c.987C>G) in the general population?

NBN p.Pro329= (c.987C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

NBN p.Pro329=

c.987C>G · rs1586075751 · VCV2003204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 1.6	GERP 1.8, phastCons 0.93
Overall
CADD	6.806	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Overall 0.000124% 2/1,613,730 alleles · ultra-rare exomes 1/1,461,502 · genomes 1/152,228 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
European (non-Finnish)	8.48e-05%	1,179,798

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.Pro329=
Coding: c.987C>G
MANE Select: NM_002485
dbSNP: rs1586075751
Type: single nucleotide variant
Location: chr8:89964417 (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.Pro329His Uncertain significance ★★ ⚠ same residue
NBN p.Pro329Leu 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
NBN c.172-2A>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-pro329 (accessed [today's date]).

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