KDM5A p.Pro523=
c.1569C>T · VCV4821667
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, 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 1 | GERP -3, phastCons 0.99 |
| Overall | ||
| CADD | 9.392 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/74,992 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00988%
Overall
0.00335%
54/1,614,006 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 4,999 |
| Admixed American | 0.00667% | 15,002 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,627 |
| European (non-Finnish) | 0.00246% | 40,688 |
| East Asian | 0.00223% | 44,876 |
| South Asian | 0.0011% | 91,074 |
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.Pro523=
- Coding
- c.1569C>T
- MANE Select
- NM_001042603
- Type
- single nucleotide variant
- Location
- chr12:333571 (GRCh38)
- Gene constraint
- LOEUF 0.27 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 70.98 · 46 PDB
- Residue 523
- 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-pro523 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown