HPSE p.Asn459=
c.1377T>C · rs11031 · VCV3037827
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 25.2%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
HPSE-related disorder
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 -0.23 | GERP -3.2 |
| Overall | ||
| CADD | 4.251 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.2%
African / African-American · 18,753/74,348 alleles
Filtering AF
24.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 24.8%
Overall
1.39%
22,418/1,607,680 alleles · common
exomes 11,315/1,455,456 · genomes 11,103/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 25.2% | 4 |
| Middle Eastern | 2.57% | 39 |
| Remaining individualsnot grpmax-eligible | 1.98% | 50 |
| Admixed American | 1.81% | 55 |
| Amishnot grpmax-eligible | 1.75% | 57 |
| Ashkenazi Jewishnot grpmax-eligible | 0.271% | 369 |
| South Asian | 0.0885% | 1,130 |
| European (non-Finnish) | 0.0846% | 1,182 |
| Finnishnot grpmax-eligible | 0.0453% | 2,207 |
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
- HPSE
- Protein
- p.Asn459=
- Coding
- c.1377T>C
- MANE Select
- NM_001098540
- dbSNP
- rs11031
- Type
- single nucleotide variant
- Location
- chr4:83301055 (GRCh38)
- Gene constraint
- LOEUF 1.066 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.02 · 58 PDB
- Residue 459
- a β-strand
Disease context
HPSE-related disorder
Similar variants
- HPSE p.Ala352= Likely benign same condition
- HPSE p.Asp476Glu Likely benign same condition
- HPSE p.His436= Likely benign same condition
- HPSE p.Lys161Gln Benign same condition
- HPSE p.Lys307Arg Benign same condition
- HPSE p.Phe236Cys Likely benign same condition
- HPSE c.673+8C>A Benign ★★ same type
- HPSE p.Gly370Asp Likely benign ★★ 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/hpse-p-asn459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown