ETHE1 p.Ser177=
c.531G>A · rs1430574021 · VCV2650063
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00348%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.1 |
| Overall | ||
| CADD | 1.529 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00348%
European (non-Finnish) · 41/1,177,578 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.00286%
46/1,607,862 alleles · very rare
exomes 45/1,455,744 · genomes 1/152,118 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00348% | 28,721 |
| South Asian | 0.00336% | 29,755 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,332 |
| African / African-American | 0.00134% | 74,850 |
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
- ETHE1
- Protein
- p.Ser177=
- Coding
- c.531G>A
- MANE Select
- NM_014297
- dbSNP
- rs1430574021
- Type
- single nucleotide variant
- Location
- chr19:43508839 (GRCh38)
- Gene constraint
- LOEUF 0.97 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.05 · 1 PDB
- Residue 177
- an α-helix
Similar variants
- ETHE1 p.Ser177Leu Uncertain significance ★ ⚠ same residue
- ETHE1 p.Ser177Trp Uncertain significance ★ ⚠ same residue
- ETHE1 c.505+1G>A Pathogenic ★★★ same type
- ETHE1 c.505+1G>T Pathogenic ★★★ same type
- ETHE1 p.Arg163Gln Pathogenic ★★★ same type
- ETHE1 p.Arg163Trp Pathogenic ★★★ same type
- ETHE1 p.Ala254Val Uncertain significance ★★★ ⚠ same type
- ETHE1 p.Arg124Leu 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/ethe1-p-ser177 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown