HDAC4 p.Val486=
c.1458C>T · rs139841625 · VCV592984
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0138%, nfe)
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 -0.75 | GERP -3.9, phastCons 0.003 |
| Overall | ||
| CADD | 4.268 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0138%
European (non-Finnish) · 163/1,179,822 alleles
Filtering AF
0.0121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.0106%
171/1,613,404 alleles · ultra-rare
exomes 168/1,461,152 · genomes 3/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0138% | 7,238 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,404 |
| African / African-American | 0.00267% | 37,477 |
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.Val486=
- Coding
- c.1458C>T
- MANE Select
- NM_001378414
- dbSNP
- rs139841625
- Type
- single nucleotide variant
- Location
- chr2:239126531 (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-val486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown