HDAC7 p.Pro33Ala
c.97C>G · rs538272411 · VCV3104645
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0163%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.136 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.6 | GERP 0.18, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 22 kb · p 0.85 · regional, not allelic |
| Overall | ||
| CADD | 17.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0163%
European (non-Finnish) · 186/1,139,470 alleles
Filtering AF
0.0143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.0126%
191/1,521,834 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0163% | 6,126 |
| Remaining individualsnot grpmax-eligible | 0.00341% | 29,363 |
| Admixed American | 0.00263% | 37,964 |
| Finnishnot grpmax-eligible | 0.00167% | 60,048 |
| South Asian | 0.00127% | 78,818 |
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
- HDAC7
- Protein
- p.Pro33Ala
- Coding
- c.97C>G
- MANE Select
- NM_015401
- dbSNP
- rs538272411
- Type
- single nucleotide variant
- Location
- chr12:47798946 (GRCh38)
- Gene constraint
- LOEUF 0.344 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.90 · 6 PDB
- Residue 33
- the 'transcription repression 1' region
Similar variants
- HDAC7 p.Arg201= Benign/Likely benign ★★ same type
- HDAC7 p.Leu233= Benign/Likely benign ★★ same type
- HDAC7 p.Thr243= Benign ★★ same type
- HDAC7 p.Ala138Val Uncertain significance ★ ⚠ same type
- HDAC7 p.Ala266Val Uncertain significance ★ ⚠ same type
- HDAC7 p.Ala337Gly Uncertain significance ★ ⚠ same type
- HDAC7 p.Ala337Thr Uncertain significance ★ ⚠ same type
- HDAC7 p.Ala431Gly 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/hdac7-p-pro33ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown