HDAC4 p.Pro645=
c.1935C>T · rs569063568 · VCV2652071
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0935%, sas)
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 -1 | GERP -3.5 |
| Overall | ||
| CADD | 5.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0935%
South Asian · 85/90,946 alleles
Filtering AF
0.0774%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0714%
Overall
0.00614%
99/1,612,410 alleles · ultra-rare
exomes 95/1,460,046 · genomes 4/152,364 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0935% | 1,070 |
| East Asian | 0.0134% | 7,477 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,804 |
| Admixed American | 0.00333% | 29,985 |
| European (non-Finnish) | 0.000254% | 393,249 |
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.Pro645=
- Coding
- c.1935C>T
- MANE Select
- NM_001378414
- dbSNP
- rs569063568
- Type
- single nucleotide variant
- Location
- chr2:239111569 (GRCh38)
- Gene constraint
- LOEUF 0.192 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.67 · 19 PDB
- Residue 645
- the 'disordered' region
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-pro645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown