ETFA p.Ala4=
c.12G>C · VCV4067425
Uncertain significance
No assertion criteria
Classification
Uncertain significance
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.66e-05%, nfe)
Conditions
1
Glutaric acidemia type 2A
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 -2 | GERP -2.6 |
| Overall | ||
| CADD | 5.347 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.66e-05%
European (non-Finnish) · 1/1,155,170 alleles
Overall
6.39e-05%
1/1,564,016 alleles · very rare
exomes 1/1,411,644 · genomes 0/152,372 · 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
- ETFA
- Protein
- p.Ala4=
- Coding
- c.12G>C
- MANE Select
- NM_000126
- Type
- single nucleotide variant
- Location
- chr15:76311377 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.00 · 4 PDB
Disease context
Glutaric acidemia type 2A
Similar variants
- ETFA p.Ala4Glu Uncertain significance ★ ⚠ same residue
- ETFA p.Ala4Val Uncertain significance ★ ⚠ same residue
- ETFA p.Arg122Lys Likely pathogenic ★★ same condition
- ETFA p.Arg18Ter Pathogenic/Likely pathogenic ★★ same condition
- ETFA p.Arg209Ter Pathogenic/Likely pathogenic ★★ same condition
- ETFA p.Arg223Ter Pathogenic/Likely pathogenic ★★ same condition
- ETFA p.Gln65Ter Likely pathogenic ★★ same condition
- ETFA p.Gly116Arg 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-p-ala4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown