HPSE2 p.Pro110=
c.330C>T · rs993031555 · VCV1630755
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0264%, eas)
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 -0.35 | GERP -3.2, phastCons 0.005 |
| Overall | ||
| CADD | 7.983 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0264%
East Asian · 11/41,592 alleles
Filtering AF
0.0148%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.000835%
13/1,557,810 alleles · ultra-rare
exomes 13/1,405,452 · genomes 0/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0264% | 3,781 |
| African / African-American | 0.00272% | 36,748 |
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.Pro110=
- Coding
- c.330C>T
- MANE Select
- NM_021828
- dbSNP
- rs993031555
- Type
- single nucleotide variant
- Location
- chr10:99232466 (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-pro110 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown