KDM5C p.Pro1508=
c.4524T>C · rs781924133 · VCV1904426
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00246%, nfe)
Conditions
1
Spastic paraplegia
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 -0.34 | GERP -2.4 |
| Overall | ||
| CADD | 1.556 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00246%
European (non-Finnish) · 22/894,083 alleles
Filtering AF
0.00161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00138%
Overall
0.00191%
23/1,207,179 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00246% | 40,640 |
| Remaining individualsnot grpmax-eligible | 0.0021% | 47,546 |
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
- KDM5C
- Protein
- p.Pro1508=
- Coding
- c.4524T>C
- MANE Select
- NM_004187
- dbSNP
- rs781924133
- Type
- single nucleotide variant
- Location
- chrX:53193126 (GRCh38)
- Structure
- AlphaFold pLDDT 72.50 · 2 PDB
- Residue 1508
- the 'disordered' region
Similar variants
- KDM5C p.Pro1508Leu Uncertain significance ★★ ⚠ same residue
- KDM5C c.1243-2A>G Pathogenic/Likely pathogenic ★★ same condition
- KDM5C p.Arg681Ter Pathogenic/Likely pathogenic ★★ same condition
- KDM5C p.Arg750Trp Likely pathogenic ★★ same condition
- KDM5C p.Arg778Ter Pathogenic ★★ same condition
- KDM5C p.Gln588Ter Pathogenic ★★ same condition
- KDM5C c.4038+6C>G Uncertain significance ★★ same condition
- KDM5C p.Ala1085Ser Uncertain significance ★★ ⚠ same condition
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/kdm5c-p-pro1508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown