Is KDM2B p.Arg18fs (c.54_58del) pathogenic?

KDM2B p.Arg18fs (c.5458del) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-22). Very rare (popmax 0.00186%, nfe); Associated with neurodevelopmental disorder.

What condition is associated with KDM2B p.Arg18fs (c.54_58del)?

KDM2B p.Arg18fs (c.54_58del) is associated with neurodevelopmental disorder (ClinVar).

How common is KDM2B p.Arg18fs (c.54_58del) in the general population?

KDM2B p.Arg18fs (c.54_58del) is very rare (popmax 0.00186%, nfe) (gnomAD).

KDM2B p.Arg18fs

c.54_58del · VCV3376850

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	GERP 0.5, phastCons 0.17

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00186% European (non-Finnish) · 22/1,179,984 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00151% 22/1,461,770 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: KDM2B
Protein: p.Arg18fs
Coding: c.54_58del
MANE Select: NM_032590
Type: Deletion
Location: chr12:121580854 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB
Residue 18: the 'disordered' region

Full KDM2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KDM2B p.Leu279fs Uncertain significance ★ same condition
KDM2B p.Thr28fs Likely benign ★★ same type
KDM2B p.Asn1002fs Pathogenic ★ same type
KDM2B p.Gln971fs Pathogenic ★ same type
KDM2B p.Ala10fs Uncertain significance ★ same type
KDM2B p.Glu22fs Uncertain significance ★ same type
KDM2B p.Gly8fs Uncertain significance ★ same type
KDM2B p.Ile1295fs Uncertain significance ★ same type

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/kdm2b-p-arg18fs (accessed [today's date]).

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