HELLS p.Ser179=
c.537G>A · VCV4695747
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, 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 0.78 | GERP -1.7, phastCons 0.96 |
| Overall | ||
| CADD | 6.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,760 alleles
Filtering AF
0.00817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00634%
Overall
0.00149%
24/1,611,152 alleles · ultra-rare
exomes 17/1,459,184 · genomes 7/151,968 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,796 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,196 |
| East Asian | 0.00223% | 44,854 |
| Finnishnot grpmax-eligible | 0.00156% | 63,990 |
| South Asian | 0.0011% | 91,020 |
| European (non-Finnish) | 0.000679% | 147,200 |
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.Ser179=
- Coding
- c.537G>A
- MANE Select
- NM_018063
- Type
- single nucleotide variant
- Location
- chr10:94574019 (GRCh38)
- Gene constraint
- LOEUF 0.587 · pLI 0.63 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 4 PDB
Similar variants
- HELLS p.Ser179Leu 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-ser179 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown