HDAC7 p.Pro807His
c.2420C>A · rs148606386 · VCV2219172
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6452 | likely pathogenic |
|---|---|---|
| REVEL | 0.492 | indeterminate |
| SaProt | LLR -12.17 | damaging |
| ⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.60 | unconstrained · MANE · 5,459 bp · p 6.7e-12 · regional, not allelic |
| Overall | ||
| CADD | 27.3 | 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.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P768H vs ClinVar P807H) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,917 |
| European (non-Finnish)grpmax | 0.00848% | 11,794 |
| Admixed American | 0.00501% | 19,957 |
| African / African-American | 0.00267% | 37,411 |
| East Asian | 0.00223% | 44,818 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- HDAC7
- Protein
- p.Pro807His
- Coding
- c.2420C>A
- MANE Select
- NM_015401
- dbSNP
- rs148606386
- Type
- single nucleotide variant
- Location
- chr12:47787745 (GRCh38)
- Gene constraint
- LOEUF 0.344 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.90 · 6 PDB
- Residue 807
- the 'histone deacetylase' region
Similar variants
- HDAC7 p.Pro807Ala Uncertain significance ★ ⚠ same residue
- HDAC7 p.Pro807Arg Uncertain significance ★ ⚠ same residue
- HDAC7 p.Pro807Ser Uncertain significance ★ ⚠ same residue
- HDAC7 p.Pro807Thr Uncertain significance ★ ⚠ same residue
- HDAC7 p.Arg201= Benign/Likely benign ★★ same type
- HDAC7 p.Leu233= Benign/Likely benign ★★ same type
- HDAC7 p.Thr243= Benign ★★ same type
- HDAC7 p.Ala138Val Uncertain significance ★ ⚠ 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/hdac7-p-pro807his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown