HDAC4 p.Ser400=
c.1200G>A · rs149580896 · VCV701809
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.43%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.01 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.9 |
| Overall | ||
| CADD | 7.656 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.43%
East Asian · 642/44,876 alleles
Filtering AF
1.34%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.3%
Overall
0.106%
1,705/1,613,938 alleles · low-frequency
exomes 1,486/1,461,670 · genomes 219/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.43% | 70 |
| Admixed American | 0.348% | 287 |
| Remaining individualsnot grpmax-eligible | 0.283% | 353 |
| African / African-American | 0.0546% | 1,830 |
| European (non-Finnish) | 0.0511% | 1,957 |
| South Asian | 0.0275% | 3,643 |
| Finnishnot grpmax-eligible | 0.0094% | 10,643 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,801 |
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.Ser400=
- Coding
- c.1200G>A
- MANE Select
- NM_001378414
- dbSNP
- rs149580896
- Type
- single nucleotide variant
- Location
- chr2:239134339 (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.Ser400Leu Likely benign ★ 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-ser400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown