HPSE2 p.Ser394=
c.1182C>T · rs372169556 · VCV722894
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0512%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.8 | GERP -3.2 |
| Overall | ||
| CADD | 8.394 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0512%
East Asian · 23/44,884 alleles
Filtering AF
0.035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0296%
Overall
0.0114%
184/1,613,790 alleles · ultra-rare
exomes 182/1,461,614 · genomes 2/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0512% | 1,951 |
| Middle Eastern | 0.0164% | 6,082 |
| European (non-Finnish) | 0.0124% | 8,081 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,409 |
| Admixed American | 0.00833% | 12,000 |
| Finnishnot grpmax-eligible | 0.00469% | 21,345 |
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.Ser394=
- Coding
- c.1182C>T
- MANE Select
- NM_021828
- dbSNP
- rs372169556
- Type
- single nucleotide variant
- Location
- chr10:98620625 (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.Ser394Phe Uncertain significance ★★ ⚠ same residue
- 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
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-ser394 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown