HDAC4 p.Ser472=
c.1416G>A · VCV4960828
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0499%, mid)
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 -8.7 | GERP -3.9 |
| Overall | ||
| CADD | 3.396 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0499%
Middle Eastern · 3/6,012 alleles
Filtering AF
0.0135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00724%
Overall
0.00223%
36/1,613,792 alleles · ultra-rare
exomes 28/1,461,462 · genomes 8/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0499% | 2,004 |
| African / African-American | 0.00666% | 15,008 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,619 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,582 |
| East Asian | 0.00223% | 44,868 |
| European (non-Finnish) | 0.00178% | 56,189 |
| South Asian | 0.0011% | 91,076 |
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.Ser472=
- Coding
- c.1416G>A
- MANE Select
- NM_001378414
- Type
- single nucleotide variant
- Location
- chr2:239126573 (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.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
- HDAC4 p.Arg13Gln 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-ser472 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown