Is KDM2B p.Ile538= (c.1614C>T) pathogenic?

KDM2B p.Ile538= (c.1614C>T) is classified Likely benign in KDM2B (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-01). Ultra-rare (popmax 0.0165%, mid).

How common is KDM2B p.Ile538= (c.1614C>T) in the general population?

KDM2B p.Ile538= (c.1614C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

KDM2B p.Ile538=

c.1614C>T · rs200296333 · VCV2643407

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 1.3	GERP -2.3, phastCons 1
Overall
CADD	13.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.0297% 479/1,613,436 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.2%	83
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Middle Easterngrpmax	0.0165%	6,062
European (non-Finnish)	0.00636%	15,733
South Asian	0.0022%	45,530
Admixed American	0.00167%	59,956
African / African-American	0.00134%	74,790

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile538=
Coding: c.1614C>T
MANE Select: NM_032590
dbSNP: rs200296333
Type: single nucleotide variant
Location: chr12:121509600 (GRCh38)
Gene constraint: LOEUF 0.266 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.20 · 4 PDB

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

Similar variants

KDM2B p.Arg614Pro Pathogenic/Likely pathogenic ★★ same type
KDM2B p.Cys616Arg Pathogenic/Likely pathogenic ★★ same type
KDM2B p.Gly638Asp Pathogenic ★★ same type
KDM2B p.Arg1124Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Arg294Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Arg612Gln Uncertain significance ★★ ⚠ same type
KDM2B p.Asn742Lys Uncertain significance ★★ ⚠ same type
KDM2B p.Glu922Lys 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-ile538 (accessed [today's date]).

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