HPSE p.His436=
c.1308T>C · rs748371922 · VCV3035311
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.116%, eas)
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 -3.3 | GERP -2.8 |
| Overall | ||
| CADD | 0.138 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.116%
East Asian · 52/44,858 alleles
Filtering AF
0.0907%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0818%
Overall
0.0036%
58/1,610,830 alleles · rare
exomes 54/1,458,510 · genomes 4/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.116% | 863 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,388 |
| European (non-Finnish) | 0.000425% | 235,403 |
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.His436=
- Coding
- c.1308T>C
- MANE Select
- NM_001098540
- dbSNP
- rs748371922
- Type
- single nucleotide variant
- Location
- chr4:83302167 (GRCh38)
- Gene constraint
- LOEUF 1.066 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.02 · 58 PDB
- Residue 436
- a β-strand
Disease context
HPSE-related disorder
Similar variants
- HPSE p.Ala352= Likely benign same condition
- HPSE p.Asn459= Benign same condition
- HPSE p.Asp476Glu 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-his436 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown