HDAC8 p.Pro22=
c.66C>G · rs2052147117 · VCV1916824
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000114%, nfe)
Conditions
1
Cornelia de Lange syndrome 5
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 -2.3 | GERP -3.1 |
| Overall | ||
| CADD | 5.804 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000114%
European (non-Finnish) · 1/876,131 alleles
Overall
9.34e-05%
1/1,071,235 alleles · very rare
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
- HDAC8
- Protein
- p.Pro22=
- Coding
- c.66C>G
- MANE Select
- NM_018486
- dbSNP
- rs2052147117
- Type
- single nucleotide variant
- Location
- chrX:72572696 (GRCh38)
- Structure
- AlphaFold pLDDT 95.45 · 53 PDB
- Residue 22
- the 'histone deacetylase' region; an α-helix
Similar variants
- HDAC8 c.165-2A>G Pathogenic ★★ same condition
- HDAC8 c.738-1G>A Pathogenic ★★ same condition
- HDAC8 c.738-2A>G Pathogenic/Likely pathogenic ★★ same condition
- HDAC8 p.Arg164Ter Pathogenic ★★ same condition
- HDAC8 p.Arg313Ter Pathogenic ★★ same condition
- HDAC8 p.Arg37Gln Pathogenic/Likely pathogenic ★★ same condition
- HDAC8 p.Asn156Ser Pathogenic ★★ same condition
- HDAC8 p.Gln263Ter Pathogenic ★★ 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/hdac8-p-pro22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown