HPSE2 p.Ala398=
c.1194T>C · rs111762231 · VCV728157
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.58%, afr)
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 1.3 | GERP -2.3, phastCons 1 |
| Overall | ||
| CADD | 8.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.58%
African / African-American · 1,186/75,022 alleles
Filtering AF
1.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.48%
Overall
0.082%
1,324/1,613,664 alleles · low-frequency
exomes 610/1,461,340 · genomes 714/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.58% | 63 |
| Admixed American | 0.108% | 923 |
| Remaining individualsnot grpmax-eligible | 0.0896% | 1,116 |
| South Asian | 0.00329% | 30,351 |
| European (non-Finnish) | 0.00119% | 84,259 |
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.Ala398=
- Coding
- c.1194T>C
- MANE Select
- NM_021828
- dbSNP
- rs111762231
- Type
- single nucleotide variant
- Location
- chr10:98620613 (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-ala398 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown