HDAC4 p.Pro424=
c.1272G>A · VCV4737858
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
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 -7.4 | GERP -3.3 |
| Overall | ||
| CADD | 0.592 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/91,078 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00888%
Overall
0.00223%
36/1,611,972 alleles · ultra-rare
exomes 29/1,459,768 · genomes 7/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,692 |
| East Asian | 0.0156% | 6,415 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,613 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| Admixed American | 0.00167% | 59,998 |
| Finnishnot grpmax-eligible | 0.00161% | 62,300 |
| African / African-American | 0.00133% | 74,910 |
| European (non-Finnish) | 0.000424% | 236,000 |
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.Pro424=
- Coding
- c.1272G>A
- MANE Select
- NM_001378414
- Type
- single nucleotide variant
- Location
- chr2:239134267 (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.Pro424Leu 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-pro424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown