HPSE2 p.Pro309=
c.927G>A · rs200916817 · VCV2955299
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, mid)
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 3.3 | GERP -2.5, phastCons 1 |
| Overall | ||
| CADD | 12.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Middle Eastern · 1/5,994 alleles
Filtering AF
0.00486%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00447%
Overall
0.00496%
80/1,613,534 alleles · ultra-rare
exomes 73/1,461,500 · genomes 7/152,034 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0167% | 5,994 |
| African / African-American | 0.00801% | 12,477 |
| European (non-Finnish) | 0.00602% | 16,618 |
| Admixed American | 0.00167% | 59,898 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,464 |
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.Pro309=
- Coding
- c.927G>A
- MANE Select
- NM_021828
- dbSNP
- rs200916817
- Type
- single nucleotide variant
- Location
- chr10:98721686 (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-pro309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown