HELLS p.Asp695=
c.2085T>C · rs2493288720 · VCV2845697
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000178%, nfe)
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 · T>G here scores Δ0.21 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.33 | GERP -2.6, phastCons 1 |
| Overall | ||
| CADD | 8.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000178%
European (non-Finnish) · 2/1,121,604 alleles
Filtering AF
3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000129%
2/1,549,994 alleles · very rare
exomes 2/1,397,724 · genomes 0/152,270 · joint denominator
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.Asp695=
- Coding
- c.2085T>C
- MANE Select
- NM_018063
- dbSNP
- rs2493288720
- Type
- single nucleotide variant
- Location
- chr10:94593612 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
- Residue 695
- 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-asp695 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown