ETFA c.963+1del
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | donor +1 | canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone |
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.5, phastCons 1 |
| Non-coding constraint | Z 1.01 | 1 kb window · o/e 0.93 · regional · uncalibrated |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.00486% | 20,581 |
| European (non-Finnish)grpmax | 0.00302% | 33,139 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- ETFA
- Coding
- c.963+1del
- MANE Select
- NM_000126
- dbSNP
- rs746488455
- Type
- Deletion
- Location
- chr15:76225848 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.00 · 4 PDB
Disease context
Also linked: multiple acyl-CoA dehydrogenase deficiencyglutaric acidemia IIa
Similar variants
- ETFA c.658_664+3del Likely pathogenic ★★ same condition
- ETFA p.Arg209fs Pathogenic/Likely pathogenic ★★ same condition
- ETFA p.Gln100fs Pathogenic/Likely pathogenic ★★ same condition
- ETFA p.Leu67_Cys68insTer Pathogenic/Likely pathogenic ★★ same condition
- ETFA p.Lys59fs Pathogenic/Likely pathogenic ★★ same condition
- ETFA c.452-11del Likely benign ★★ same condition
- ETFA c.665-17del Benign/Likely benign ★★ same condition
- ETFA c.664+1_664+2del Likely pathogenic ★ same condition
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/etfa-c-963-plus-1del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown