HDAC4 p.Pro651=
c.1953C>T · rs146056747 · VCV281906
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.874%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -3.5 |
| Overall | ||
| CADD | 2.872 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.874%
African / African-American · 656/75,052 alleles
Filtering AF
0.819%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.797%
Overall
0.0548%
884/1,612,410 alleles · rare
exomes 474/1,460,056 · genomes 410/152,354 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.874% | 114 |
| Middle Eastern | 0.135% | 742 |
| Admixed American | 0.115% | 869 |
| Remaining individualsnot grpmax-eligible | 0.0689% | 1,451 |
| European (non-Finnish) | 0.00915% | 10,924 |
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
- HDAC4
- Protein
- p.Pro651=
- Coding
- c.1953C>T
- MANE Select
- NM_001378414
- dbSNP
- rs146056747
- Type
- single nucleotide variant
- Location
- chr2:239111551 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.67 · 19 PDB
Similar variants
- HDAC4 p.Pro651Ser Likely benign ★ same residue
- HDAC4 p.Pro248Leu Pathogenic ★★ same type
- HDAC4 p.Thr244Lys Pathogenic/Likely pathogenic ★★ same type
- HDAC4 c.865+8G>A Uncertain significance ★★ same type
- HDAC4 p.Ala445Thr Uncertain significance ★★ ⚠ same type
- HDAC4 p.Ala620Thr Uncertain significance ★★ ⚠ same type
- HDAC4 p.Ala91Thr Uncertain significance ★★ ⚠ same type
- HDAC4 p.Arg132Trp 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/hdac4-p-pro651 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown