HELLS c.2422+21del
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0177%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +21 | near-intronic (+21 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.73 | GERP 0.014 |
| Non-coding constraint | Z 2.35 | 1 kb window · o/e 0.83 · regional · uncalibrated |
| Overall | ||
| CADD | 1.113 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0177%
Admixed American · 10/56,386 alleles
Filtering AF
0.00953%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0073%
Overall
0.00579%
86/1,484,064 alleles · ultra-rare
exomes 84/1,332,468 · genomes 2/151,596 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0177% | 5,639 |
| Middle Eastern | 0.0173% | 5,766 |
| Remaining individualsnot grpmax-eligible | 0.0069% | 14,482 |
| European (non-Finnish) | 0.00589% | 16,991 |
| South Asian | 0.00586% | 17,052 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00353% | 28,314 |
| African / African-American | 0.00278% | 35,910 |
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
- HELLS
- Coding
- c.2422+21del
- MANE Select
- NM_018063
- dbSNP
- rs756021887
- Type
- Deletion
- Location
- chr10:94597125 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
Similar variants
- HELLS p.Arg129fs Pathogenic ★ same type
- HELLS p.Glu239fs Pathogenic ★ same type
- HELLS p.Ser164_Ser165insTer Likely pathogenic ★ same type
- HELLS p.Glu157del Uncertain significance ★ same type
- HELLS p.Lys156del Uncertain significance ★ same type
- HELLS c.1033-5del Benign ★ same type
- HELLS c.1767+18_1767+23del Likely benign ★ same type
- HELLS c.1768-6_1768-4del Likely benign ★ 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/hells-c-2422-plus-21del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown