HELLS p.Glu146=
c.438A>G · rs555751938 · VCV2883433
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00464%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.05 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 5.4 | GERP 0.73, phastCons 1 |
| Overall | ||
| CADD | 13.25 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00464%
South Asian · 4/86,186 alleles
Filtering AF
0.00158%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00093%
Overall
0.000404%
6/1,486,788 alleles · very rare
exomes 5/1,334,498 · genomes 1/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00464% | 21,546 |
| European (non-Finnish) | 0.000186% | 538,834 |
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
- Protein
- p.Glu146=
- Coding
- c.438A>G
- MANE Select
- NM_018063
- dbSNP
- rs555751938
- Type
- single nucleotide variant
- Location
- chr10:94571390 (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-p-glu146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown