HELLS c.2248+15T>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0335%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +15 | near-intronic (+15 nt from the splice site) |
|---|---|---|
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.66 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -1.3 | GERP -2.5 |
| Non-coding constraint | Z 2.90 | 1 kb window · o/e 0.76 · regional · uncalibrated |
| Overall | ||
| CADD | 1.405 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0335%
Middle Eastern · 2/5,974 alleles
Filtering AF
0.0059%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00245%
Overall
0.00197%
31/1,572,000 alleles · ultra-rare
exomes 29/1,419,832 · genomes 2/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0335% | 2,987 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0276% | 3,620 |
| East Asian | 0.00672% | 14,871 |
| European (non-Finnish) | 0.0014% | 71,618 |
| African / African-American | 0.00136% | 73,686 |
| South Asian | 0.00112% | 89,416 |
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.2248+15T>C
- MANE Select
- NM_018063
- dbSNP
- rs773817818
- Type
- single nucleotide variant
- Location
- chr10:94594869 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
Similar variants
- HELLS c.370+2T>A Pathogenic ★★ same type
- HELLS c.1488+4T>C Uncertain significance ★★ same type
- HELLS p.Ala16Pro Uncertain significance ★★ ⚠ same type
- HELLS p.Arg319Trp Uncertain significance ★★ ⚠ same type
- HELLS p.Arg507Gln Uncertain significance ★★ ⚠ same type
- HELLS p.Arg513Gly Uncertain significance ★★ ⚠ same type
- HELLS p.Arg541Gln Uncertain significance ★★ ⚠ same type
- HELLS p.Arg5Trp 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/hells-c-2248-plus-15t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown