HDAC6 p.His652=
c.1956C>T · rs368341039 · VCV739524
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0586%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.50 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.4 | GERP -1.2 |
| Overall | ||
| CADD | 1.582 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0586%
Middle Eastern · 2/3,411 alleles
Filtering AF
0.0104%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00457%
Overall
0.00559%
67/1,198,238 alleles · ultra-rare
exomes 59/1,085,650 · genomes 8/112,588 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0586% | 1,706 |
| European (non-Finnish) | 0.00641% | 15,605 |
| Remaining individualsnot grpmax-eligible | 0.00636% | 15,714 |
| Admixed American | 0.00453% | 22,095 |
| East Asian | 0.00298% | 33,513 |
| Finnishnot grpmax-eligible | 0.00217% | 46,036 |
| South Asian | 0.00183% | 54,712 |
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
- HDAC6
- Protein
- p.His652=
- Coding
- c.1956C>T
- MANE Select
- NM_006044
- dbSNP
- rs368341039
- Type
- single nucleotide variant
- Location
- chrX:48818071 (GRCh38)
- Structure
- AlphaFold pLDDT 77.66 · 22 PDB
- Residue 652
- the 'histone deacetylase 2' region
Similar variants
- HDAC6 p.Ala374Gly Uncertain significance ★★ ⚠ same type
- HDAC6 c.1059+6G>C Likely benign ★★ same type
- HDAC6 c.2187+20G>A Benign ★★ same type
- HDAC6 p.Glu1017= Benign/Likely benign ★★ same type
- HDAC6 p.Glu889= Benign ★★ same type
- HDAC6 p.Gly1051= Benign/Likely benign ★★ same type
- HDAC6 p.Gly1083Asp Likely benign ★★ same type
- HDAC6 p.Gly930Arg Likely benign ★★ 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/hdac6-p-his652 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown