Is KDM2B p.Arg16Ter (c.46C>T) pathogenic?

KDM2B p.Arg16Ter (c.46C>T) is classified Uncertain significance in KDM2B (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-29). Ultra-rare (popmax 0.0167%, amr).

How common is KDM2B p.Arg16Ter (c.46C>T) in the general population?

KDM2B p.Arg16Ter (c.46C>T) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

KDM2B p.Arg16Ter

c.46C>T · rs376781406 · VCV403007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.75	GERP -0.46, phastCons 0.84
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% Admixed American · 10/59,964 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00682%

Overall 0.00366% 59/1,613,642 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	5,996
Remaining individualsnot grpmax-eligible	0.008%	12,494
African / African-American	0.00401%	24,953
European (non-Finnish)	0.00347%	28,778

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.Arg16Ter
Coding: c.46C>T
dbSNP: rs376781406
Type: single nucleotide variant
Location: chr12:121580866 (GRCh38)

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

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-arg16ter (accessed [today's date]).

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