Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 10.4%, amr) — too common for a highly-penetrant pathogenic allele
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 -1.5 | GERP -3.8 |
| Overall | ||
| CADD | 6.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.4%
Admixed American · 5,816/55,994 alleles
Filtering AF
10.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.1%
Overall
3.02%
47,462/1,570,388 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 10.4% | 10 |
| African / African-American | 8.85% | 11 |
| East Asian | 5.56% | 18 |
| Ashkenazi Jewishnot grpmax-eligible | 4.82% | 21 |
| Remaining individualsnot grpmax-eligible | 3.53% | 28 |
| Amishnot grpmax-eligible | 3.41% | 29 |
| Middle Eastern | 3% | 33 |
| South Asian | 2.62% | 38 |
| Finnishnot grpmax-eligible | 2.47% | 41 |
| European (non-Finnish) | 2.18% | 46 |
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
- KDM4E
- Protein
- p.Thr190=
- Coding
- c.570A>G
- MANE Select
- NM_001161630
- dbSNP
- rs2848447
- Type
- single nucleotide variant
- Location
- chr11:95026127 (GRCh38)
- Structure
- AlphaFold pLDDT 76.85 · 1 PDB
- Residue 190
- the jmjc domain
Similar variants
- KDM4E p.Ala187= Likely benign ★★ same type
- KDM4E p.Cys381Tyr Benign ★★ same type
- KDM4E p.Gln42Arg Benign ★★ same type
- KDM4E p.Ala224Asp Uncertain significance ★ ⚠ same type
- KDM4E p.Ala265Val Uncertain significance ★ ⚠ same type
- KDM4E p.Ala287Thr Uncertain significance ★ same type
- KDM4E p.Ala406Thr Uncertain significance ★ ⚠ same type
- KDM4E p.Arg100Cys 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/kdm4e-p-thr190 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown