HPSE2 p.Val432=
c.1296G>C · VCV3589484
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 2.8 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 7.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,018 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000186%
3/1,613,408 alleles · very rare
exomes 3/1,461,176 · genomes 0/152,232 · joint denominator
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.Val432=
- Coding
- c.1296G>C
- MANE Select
- NM_021828
- Type
- single nucleotide variant
- Location
- chr10:98614928 (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 p.Val432Met Uncertain significance ★ ⚠ same residue
- 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
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-val432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown