HELLS p.Asn697=
c.2091C>T · rs1473532539 · VCV724893
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00353%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.87 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.454 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00353%
Admixed American · 2/56,624 alleles
Filtering AF
0.000586%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000261%
Overall
0.000687%
11/1,601,246 alleles · very rare
exomes 11/1,449,042 · genomes 0/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00353% | 28,312 |
| European (non-Finnish) | 0.000766% | 130,562 |
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.Asn697=
- Coding
- c.2091C>T
- MANE Select
- NM_018063
- dbSNP
- rs1473532539
- Type
- single nucleotide variant
- Location
- chr10:94594697 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
- Residue 697
- 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-asn697 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown