HELLS p.Ala342=
c.1026G>A · rs373919239 · VCV1596774
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0242%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.7 | GERP -1.3 |
| Overall | ||
| CADD | 7.604 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0242%
African / African-American · 18/74,470 alleles
Filtering AF
0.0156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.00181%
29/1,604,034 alleles · ultra-rare
exomes 16/1,451,748 · genomes 13/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0242% | 4,137 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,038 |
| Finnishnot grpmax-eligible | 0.00313% | 31,938 |
| South Asian | 0.00224% | 44,641 |
| Admixed American | 0.00174% | 57,404 |
| European (non-Finnish) | 0.00034% | 294,015 |
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.Ala342=
- Coding
- c.1026G>A
- MANE Select
- NM_018063
- dbSNP
- rs373919239
- Type
- single nucleotide variant
- Location
- chr10:94576799 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
- Residue 342
- the helicase atp-binding domain
Similar variants
- HELLS p.Ala342Val Uncertain significance ★ ⚠ same residue
- 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
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-ala342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown