KDM5C p.Arg748Pro
c.2243G>C · rs797045640 · VCV211246
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9991 | likely pathogenic · top 3% in KDM5C |
|---|---|---|
| REVEL | 0.897 | moderately pathogenic-leaning |
| SaProt | LLR -13.71 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.27 | loss · gain 0.03 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.42 | unconstrained · MANE · 2,828 bp · p 1e-08 · regional, not allelic |
| Overall | ||
| CADD | 29.8 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- KDM5C
- Protein
- p.Arg748Pro
- Coding
- c.2243G>C
- MANE Select
- NM_004187
- dbSNP
- rs797045640
- Type
- single nucleotide variant
- Location
- chrX:53198977 (GRCh38)
- Structure
- AlphaFold pLDDT 72.50 · 2 PDB
- Residue 748
- a β-strand
Similar variants
- KDM5C p.Arg748Trp Uncertain significance ★ ⚠ same residue
- KDM5C c.1243-2A>G Pathogenic/Likely pathogenic ★★ same type
- KDM5C p.Arg332Ter Pathogenic ★★ same type
- KDM5C p.Arg599Cys Pathogenic/Likely pathogenic ★★ same type
- KDM5C p.Arg681Ter Pathogenic/Likely pathogenic ★★ same type
- KDM5C p.Arg68Ter Pathogenic ★★ same type
- KDM5C p.Arg750Trp Likely pathogenic ★★ same type
- KDM5C p.Arg778Ter Pathogenic ★★ 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/kdm5c-p-arg748pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown