KDM4B p.Pro418=
c.1254C>G · VCV4821541
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.275%, afr)
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 -11 | GERP -2.7 |
| Overall | ||
| CADD | 1.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.275%
African / African-American · 201/72,980 alleles
Filtering AF
0.244%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.232%
Overall
0.0139%
214/1,542,414 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.275% | 363 |
| Remaining individualsnot grpmax-eligible | 0.0151% | 6,632 |
| Admixed American | 0.00399% | 25,089 |
| European (non-Finnish) | 0.000175% | 571,592 |
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.Pro418=
- Coding
- c.1254C>G
- MANE Select
- NM_015015
- Type
- single nucleotide variant
- Location
- chr19:5119791 (GRCh38)
- Gene constraint
- LOEUF 0.371 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.50 · 6 PDB
- Residue 418
- 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-pro418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown