ETFA c.451+253A>G
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.45%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +253 | deep intronic (+253 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.096 | GERP -2, phastCons 0.06 |
| Non-coding constraint | Z 0.69 | 1 kb window · o/e 0.94 · regional · uncalibrated |
| Overall | ||
| CADD | 13.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.45%
African / African-American · 603/41,556 alleles
Filtering AF
1.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.32%
Overall
0.412%
628/152,306 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.45% | 69 |
| Remaining individualsnot grpmax-eligible | 0.426% | 235 |
| Admixed American | 0.098% | 1,020 |
| European (non-Finnish) | 0.00147% | 68,030 |
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.451+253A>G
- MANE Select
- NM_000126
- dbSNP
- rs115309755
- Type
- single nucleotide variant
- Location
- chr15:76287593 (GRCh38)
- Gene constraint
- LOEUF 1.166 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.00 · 4 PDB
Similar variants
- ETFA c.186+1G>A Likely pathogenic ★★ same type
- ETFA c.39+1G>A Likely pathogenic ★★ same type
- ETFA c.451+1G>A Likely pathogenic ★★ same type
- ETFA c.452-2A>G Likely pathogenic ★★ same type
- ETFA c.664+1G>A Likely pathogenic ★★ same type
- ETFA c.665-1G>A Likely pathogenic ★★ same type
- ETFA p.Arg122Lys Likely pathogenic ★★ same type
- ETFA p.Arg18Ter Pathogenic/Likely pathogenic ★★ 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/etfa-c-451-plus-253a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown