KDM5C p.Pro1223=
c.3669G>A · rs2146822099 · VCV1133455
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.023%, mid)
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 -5.3 | GERP -3.8 |
| Overall | ||
| CADD | 0.032 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.023%
Middle Eastern · 1/4,350 alleles
Filtering AF
0.000325%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000209%
Overall
0.000729%
8/1,097,154 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.023% | 4,350 |
| European (non-Finnish) | 0.000782% | 127,862 |
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.Pro1223=
- Coding
- c.3669G>A
- MANE Select
- NM_004187
- dbSNP
- rs2146822099
- Type
- single nucleotide variant
- Location
- chrX:53194508 (GRCh38)
- Structure
- AlphaFold pLDDT 72.50 · 2 PDB
Similar variants
- KDM5C p.Pro1223Leu 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-pro1223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown