HPSE2 p.Glu191=
c.573G>A · rs148098032 · VCV716933
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.215%, mid)
Conditions
1
urofacial syndrome type 1
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 -0.89 | GERP 1, phastCons 0.002 |
| Overall | ||
| CADD | 6.662 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.215%
Middle Eastern · 13/6,058 alleles
Filtering AF
0.156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.147%
Overall
0.0382%
616/1,614,070 alleles · rare
exomes 545/1,461,762 · genomes 71/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.215% | 466 |
| South Asian | 0.178% | 562 |
| Admixed American | 0.115% | 870 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| European (non-Finnish) | 0.028% | 3,576 |
| African / African-American | 0.0253% | 3,950 |
| Finnishnot grpmax-eligible | 0.00156% | 63,954 |
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.Glu191=
- Coding
- c.573G>A
- MANE Select
- NM_021828
- dbSNP
- rs148098032
- Type
- single nucleotide variant
- Location
- chr10:99144275 (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 condition
- HPSE2 c.291-1G>T Likely pathogenic ★★ same condition
- HPSE2 p.Arg153Ter Pathogenic/Likely pathogenic ★★ same condition
- HPSE2 p.Arg506Ter Pathogenic/Likely pathogenic ★★ same condition
- HPSE2 p.Arg267Trp Uncertain significance ★★ same condition
- HPSE2 p.Arg272Gln Uncertain significance ★★ ⚠ same condition
- HPSE2 p.Arg494His Uncertain significance ★★ ⚠ same condition
- HPSE2 p.Arg494Leu Uncertain significance ★★ same condition
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-glu191 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown