HSF4 p.Asp30=
c.90C>T · rs34623497 · VCV707254
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0689%, 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 2.2 | GERP -0.084, phastCons 1 |
| Overall | ||
| CADD | 13.71 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0689%
Middle Eastern · 4/5,806 alleles
Filtering AF
0.0235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0142%
Overall
0.00839%
135/1,608,176 alleles · ultra-rare
exomes 124/1,455,908 · genomes 11/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0689% | 1,452 |
| African / African-American | 0.0173% | 5,771 |
| Admixed American | 0.0151% | 6,644 |
| Remaining individualsnot grpmax-eligible | 0.0145% | 6,920 |
| South Asian | 0.011% | 9,054 |
| European (non-Finnish) | 0.00763% | 13,102 |
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
- HSF4
- Protein
- p.Asp30=
- Coding
- c.90C>T
- MANE Select
- NM_001374675
- dbSNP
- rs34623497
- Type
- single nucleotide variant
- Location
- chr16:67164901 (GRCh38)
- Gene constraint
- LOEUF 1.111 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 61.04 · 2 PDB
- Residue 30
- a DNA-binding region
Similar variants
- HSF4 p.Asp30fs Pathogenic ★ same residue
- HSF4 p.Ala320Gly Uncertain significance ★★ ⚠ same type
- HSF4 p.Ala432Val Uncertain significance ★★ ⚠ same type
- HSF4 p.Arg108Ser Uncertain significance ★★ ⚠ same type
- HSF4 p.Glu115Gly Uncertain significance ★★ ⚠ same type
- HSF4 p.Glu247= Uncertain significance ★★ same type
- HSF4 p.Glu3Gly Uncertain significance ★★ ⚠ same type
- HSF4 p.Gly13Asp 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/hsf4-p-asp30 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown