HSF1 p.Ser320=
c.960C>T · rs143898779 · VCV2658978
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.122%, 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 -7.8 | GERP -2.6 |
| Overall | ||
| CADD | 1.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.122%
South Asian · 111/91,072 alleles
Filtering AF
0.103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0965%
Overall
0.0156%
252/1,612,332 alleles · rare
exomes 220/1,460,136 · genomes 32/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.122% | 820 |
| European (non-Finnish) | 0.0105% | 9,514 |
| Admixed American | 0.00833% | 11,999 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,616 |
| African / African-American | 0.00533% | 18,753 |
| Finnishnot grpmax-eligible | 0.00479% | 20,869 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,580 |
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
- HSF1
- Protein
- p.Ser320=
- Coding
- c.960C>T
- MANE Select
- NM_005526
- dbSNP
- rs143898779
- Type
- single nucleotide variant
- Location
- chr8:144312062 (GRCh38)
- Gene constraint
- LOEUF 0.884 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.61 · 8 PDB
- Residue 320
- a modified residue (phosphoserine; by pka); the 'disordered' region
Similar variants
- HSF1 p.Asp143= Benign ★★ same type
- HSF1 p.Thr24= Benign ★★ same type
- HSF1 p.Ala160Thr Uncertain significance ★ ⚠ same type
- HSF1 p.Ala173Thr Uncertain significance ★ ⚠ same type
- HSF1 p.Ala313Glu Uncertain significance ★ ⚠ same type
- HSF1 p.Ala343Thr Uncertain significance ★ ⚠ same type
- HSF1 p.Ala437Thr Uncertain significance ★ ⚠ same type
- HSF1 p.Ala470Glu 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/hsf1-p-ser320 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown