HPSE2 c.784+7A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +7 | near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2, phastCons 1 |
| Non-coding constraint | Z 1.75 | 1 kb window · o/e 0.85 · regional · uncalibrated |
| Overall | ||
| CADD | 16.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,012 alleles
Filtering AF
0.00661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00482%
Overall
0.000558%
9/1,612,484 alleles · ultra-rare
exomes 9/1,460,166 · genomes 0/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,501 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
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
- Coding
- c.784+7A>G
- MANE Select
- NM_021828
- dbSNP
- rs1182874300
- Type
- single nucleotide variant
- Location
- chr10:98743876 (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-c-784-plus-7a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown