HDAC4 p.Ser290=
c.870C>T · rs552983427 · VCV706143
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.746%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.033 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.2 |
| Overall | ||
| CADD | 0.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.746%
South Asian · 679/91,076 alleles
Filtering AF
0.699%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.68%
Overall
0.0451%
728/1,612,936 alleles · rare
exomes 699/1,461,278 · genomes 29/151,658 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.746% | 134 |
| Middle Eastern | 0.0495% | 2,020 |
| Remaining individualsnot grpmax-eligible | 0.032% | 3,125 |
| East Asian | 0.00446% | 22,438 |
| European (non-Finnish) | 0.00203% | 49,151 |
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.Ser290=
- Coding
- c.870C>T
- MANE Select
- NM_001378414
- dbSNP
- rs552983427
- Type
- single nucleotide variant
- Location
- chr2:239139792 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.67 · 19 PDB
- Residue 290
- the 'interaction with mef2a' region; the 'disordered' region
Similar variants
- HDAC4 p.Ser290Pro Uncertain significance ★ ⚠ 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-ser290 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown