HDAC2 p.Val289=
c.867A>T · rs77438668 · VCV782745
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.48%, afr)
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 -2.1 | GERP -3.8 |
| Overall | ||
| CADD | 5.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.48%
African / African-American · 360/75,042 alleles
Filtering AF
0.439%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.423%
Overall
0.0505%
815/1,613,470 alleles · rare
exomes 595/1,461,140 · genomes 220/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.48% | 208 |
| Ashkenazi Jewishnot grpmax-eligible | 0.365% | 274 |
| Middle Eastern | 0.215% | 466 |
| Remaining individualsnot grpmax-eligible | 0.12% | 833 |
| Admixed American | 0.115% | 870 |
| European (non-Finnish) | 0.0158% | 6,341 |
| South Asian | 0.00439% | 22,766 |
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
- HDAC2
- Protein
- p.Val289=
- Coding
- c.867A>T
- MANE Select
- NM_001527
- dbSNP
- rs77438668
- Type
- single nucleotide variant
- Location
- chr6:113946123 (GRCh38)
- Gene constraint
- LOEUF 0.367 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 86.01 · 48 PDB
- Residue 289
- the 'histone deacetylase' region; an α-helix
Similar variants
- HDAC2 p.Ala320Gly Uncertain significance ★ ⚠ same type
- HDAC2 p.Arg78Gln Uncertain significance ★ ⚠ same type
- HDAC2 p.Asp182Gly Uncertain significance ★ ⚠ same type
- HDAC2 p.Asp234Tyr Uncertain significance ★ ⚠ same type
- HDAC2 p.Asp423Asn Uncertain significance ★ ⚠ same type
- HDAC2 p.Asp465Glu Uncertain significance ★ ⚠ same type
- HDAC2 p.Cys262Tyr Uncertain significance ★ ⚠ same type
- HDAC2 p.Gln240His 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/hdac2-p-val289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown