HELLS p.Asp706=
c.2118T>C · rs77176332 · VCV786170
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.17%, 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 -0.28 | GERP -2.2, phastCons 0.43 |
| Overall | ||
| CADD | 6.272 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.17%
African / African-American · 877/75,048 alleles
Filtering AF
1.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.08%
Overall
0.0611%
986/1,613,872 alleles · low-frequency
exomes 500/1,461,546 · genomes 486/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.17% | 86 |
| Remaining individualsnot grpmax-eligible | 0.0736% | 1,359 |
| Admixed American | 0.065% | 1,538 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00439% | 22,766 |
| European (non-Finnish) | 0.00161% | 62,094 |
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.Asp706=
- Coding
- c.2118T>C
- MANE Select
- NM_018063
- dbSNP
- rs77176332
- Type
- single nucleotide variant
- Location
- chr10:94594724 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
- Residue 706
- the helicase c-terminal domain
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-asp706 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown