KDM5A p.Pro469=
c.1407G>A · VCV4083940
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, 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 -10 | GERP -5 |
| Overall | ||
| CADD | 5.113 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,880 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.00116%
17/1,461,768 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,440 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| South Asian | 0.0022% | 45,545 |
| Admixed American | 0.00167% | 60,000 |
| Finnishnot grpmax-eligible | 0.00156% | 64,012 |
| African / African-American | 0.00133% | 74,908 |
| European (non-Finnish) | 0.000678% | 147,493 |
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
- KDM5A
- Protein
- p.Pro469=
- Coding
- c.1407G>A
- MANE Select
- NM_001042603
- Type
- single nucleotide variant
- Location
- chr12:334324 (GRCh38)
- Gene constraint
- LOEUF 0.27 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.98 · 46 PDB
- Residue 469
- the jmjc domain
Similar variants
- KDM5A c.4074+1G>A Likely pathogenic ★★ same type
- KDM5A p.Ala1260Val Uncertain significance ★★ ⚠ same type
- KDM5A p.Ala736Thr Uncertain significance ★★ ⚠ same type
- KDM5A p.Glu1021Gly Uncertain significance ★★ ⚠ same type
- KDM5A p.Gly630Glu Uncertain significance ★★ ⚠ same type
- KDM5A p.Ile1011Thr Uncertain significance ★★ ⚠ same type
- KDM5A p.Ser479Cys Uncertain significance ★★ ⚠ same type
- KDM5A p.Ser572Cys 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/kdm5a-p-pro469 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown