KDM4B p.Ser452=
c.1356C>T · VCV4534209
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.332%, eas)
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 -4.6 | GERP -2.4 |
| Overall | ||
| CADD | 3.319 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.332%
East Asian · 146/43,970 alleles
Filtering AF
0.288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.271%
Overall
0.0307%
468/1,525,288 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.332% | 301 |
| Remaining individualsnot grpmax-eligible | 0.0632% | 1,581 |
| European (non-Finnish) | 0.0236% | 4,238 |
| Admixed American | 0.0126% | 7,953 |
| African / African-American | 0.0111% | 9,030 |
| South Asian | 0.00258% | 38,730 |
| Finnishnot grpmax-eligible | 0.00169% | 59,202 |
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
- KDM4B
- Protein
- p.Ser452=
- Coding
- c.1356C>T
- MANE Select
- NM_015015
- Type
- single nucleotide variant
- Location
- chr19:5131116 (GRCh38)
- Gene constraint
- LOEUF 0.371 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.50 · 6 PDB
- Residue 452
- the 'disordered' region
Similar variants
- KDM4B c.432+1G>A Pathogenic/Likely pathogenic ★★ same type
- KDM4B p.His768Arg Likely pathogenic ★★ same type
- KDM4B p.Ala187Thr Uncertain significance ★★ ⚠ same type
- KDM4B p.Ala651Asp Uncertain significance ★★ ⚠ same type
- KDM4B p.Ala706Gly Uncertain significance ★★ ⚠ same type
- KDM4B p.Ala759Thr Uncertain significance ★★ ⚠ same type
- KDM4B p.Arg1020His Uncertain significance ★★ ⚠ same type
- KDM4B p.Arg1035Cys 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/kdm4b-p-ser452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown