Is NBN p.Ser72fs (c.215del) pathogenic?

NBN p.Ser72fs (c.215del) is classified Likely pathogenic in NBN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). Very rare (popmax 0.0011%, sas); Associated with aplastic anemia.

What condition is associated with NBN p.Ser72fs (c.215del)?

NBN p.Ser72fs (c.215del) is associated with aplastic anemia (ClinVar).

How common is NBN p.Ser72fs (c.215del) in the general population?

NBN p.Ser72fs (c.215del) is very rare (popmax 0.0011%, sas) (gnomAD).

NBN p.Ser72fs

c.215del · rs1563581276 · VCV3239831

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

aplastic anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.95	GERP -0.76, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,052 alleles

Overall 6.84e-05% 1/1,461,100 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.Ser72fs
Coding: c.215del
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1563581276
Type: Deletion
Location: chr8:89981480 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 72: the 'disordered' region

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

Disease context

aplastic anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NBN p.Ser72del Uncertain significance ★ same residue
NBN c.1397+1del Pathogenic ★★ same condition
NBN c.163_171+3del Pathogenic/Likely pathogenic ★★ same condition
NBN c.2071del Pathogenic/Likely pathogenic ★★ same condition
NBN p.Ala446fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Arg551fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Asn419fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Asn684fs Pathogenic/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-ser72fs (accessed [today's date]).

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