HDAC4 p.Pro228=
c.684G>A · rs144387989 · VCV284218
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
rare (popmax 0.362%, nfe)
Conditions
1
2q37 microdeletion syndrome
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 -20 | GERP -5.4 |
| Overall | ||
| CADD | 5.914 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.362%
European (non-Finnish) · 4,269/1,180,026 alleles
Filtering AF
0.353%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.349%
Overall
0.29%
4,682/1,614,110 alleles · rare
exomes 4,408/1,461,878 · genomes 274/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.362% | 276 |
| Remaining individualsnot grpmax-eligible | 0.277% | 361 |
| Admixed American | 0.163% | 612 |
| Finnishnot grpmax-eligible | 0.109% | 915 |
| African / African-American | 0.056% | 1,786 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0242% | 4,140 |
| East Asian | 0.0111% | 8,973 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
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.Pro228=
- Coding
- c.684G>A
- MANE Select
- NM_001378414
- dbSNP
- rs144387989
- Type
- single nucleotide variant
- Location
- chr2:239156701 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.67 · 19 PDB
- Residue 228
- the 'interaction with mef2a' region
Similar variants
- HDAC4 p.Pro248Leu Pathogenic ★★ same condition
- HDAC4 p.Pro550Leu Uncertain significance ★★ ⚠ same condition
- HDAC4 p.Pro583Leu Uncertain significance ★★ ⚠ same condition
- HDAC4 c.1534-9G>A Likely benign ★★ same condition
- HDAC4 c.2532+18G>A Likely benign ★★ same condition
- HDAC4 p.Ala37= Benign/Likely benign ★★ same condition
- HDAC4 p.Ala791Thr Benign/Likely benign ★★ ⚠ same condition
- HDAC4 p.Glu603= Benign/Likely benign ★★ same condition
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-pro228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown