HPSE2 p.Tyr28=
c.84C>T · rs200734371 · VCV2166366
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0625%, eas)
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 6.8 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 11.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0625%
East Asian · 28/44,830 alleles
Filtering AF
0.0443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0383%
Overall
0.00248%
40/1,614,058 alleles · ultra-rare
exomes 29/1,461,882 · genomes 11/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0625% | 1,601 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| South Asian | 0.00659% | 15,178 |
| European (non-Finnish) | 8.47e-05% | 1,180,012 |
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
- HPSE2
- Protein
- p.Tyr28=
- Coding
- c.84C>T
- MANE Select
- NM_021828
- dbSNP
- rs200734371
- Type
- single nucleotide variant
- Location
- chr10:99235719 (GRCh38)
- Gene constraint
- LOEUF 0.837 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.90
Similar variants
- HPSE2 c.1099-1G>A Pathogenic ★★ same type
- HPSE2 c.291-1G>T Likely pathogenic ★★ same type
- HPSE2 p.Arg153Ter Pathogenic/Likely pathogenic ★★ same type
- HPSE2 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same type
- HPSE2 p.Arg267Trp Uncertain significance ★★ same type
- HPSE2 p.Arg272Gln Uncertain significance ★★ ⚠ same type
- HPSE2 p.Arg352His Uncertain significance ★★ ⚠ same type
- HPSE2 p.Arg494His 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/hpse2-p-tyr28 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown