KDM5C p.Ala683=
c.2049C>T · rs1169859502 · VCV2660594
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
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 1.2 | GERP -0.31, phastCons 1 |
| Overall | ||
| CADD | 7.749 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,372 alleles
Filtering AF
3.7e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.4e-05%
Overall
0.000331%
4/1,209,444 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0229% | 4,372 |
| South Asian | 0.00176% | 56,826 |
| European (non-Finnish) | 0.000223% | 447,443 |
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.Ala683=
- Coding
- c.2049C>T
- MANE Select
- NM_004187
- dbSNP
- rs1169859502
- Type
- single nucleotide variant
- Location
- chrX:53201562 (GRCh38)
- Structure
- AlphaFold pLDDT 72.50 · 2 PDB
- Residue 683
- an α-helix
Similar variants
- KDM5C p.Ala683Val 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-ala683 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown