Is NBN p.Pro198fs (c.591_603delinsTTG) pathogenic?

NBN p.Pro198fs (c.591603delinsTTG) is classified Pathogenic/Likely pathogenic in NBN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-07-01). Absent from gnomAD; Associated with acute lymphoblastic leukemia.

What condition is associated with NBN p.Pro198fs (c.591_603delinsTTG)?

NBN p.Pro198fs (c.591_603delinsTTG) is associated with acute lymphoblastic leukemia, Nijmegen breakage syndrome, hereditary neoplastic syndrome (ClinVar).

How common is NBN p.Pro198fs (c.591_603delinsTTG) in the general population?

NBN p.Pro198fs (c.591_603delinsTTG) is absent from gnomAD (gnomAD).

NBN p.Pro198fs

c.591_603delinsTTG · rs1554564297 · VCV481871

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

acute lymphoblastic leukemia

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 5.9	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NBN
Protein: p.Pro198fs
Coding: c.591_603delinsTTG
MANE Select: NM_057091 · reported on NM_002485
dbSNP: rs1554564297
Type: Indel
Location: chr8:89971272 (GRCh38)
Structure: AlphaFold pLDDT 75.83 · 5 PDB
Residue 198: a disulfide bond; a β-strand

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.Pro198Arg Uncertain significance ★★ ⚠ same residue
NBN p.Pro198Leu Uncertain significance ★★ ⚠ same residue
NBN p.Pro198Ser Uncertain significance ★★ ⚠ same residue
NBN c.585-1_585delinsC Likely pathogenic ★★ same condition
NBN p.Glu179fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Pro495fs Pathogenic/Likely pathogenic ★★ same condition
NBN p.Gln451Pro Uncertain significance ★★ same condition
NBN p.His711_His712delinsLeuTyr Uncertain significance ★★ 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-pro198fs (accessed [today's date]).

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