ERF p.Ala415del
c.1243_1245del · rs759202471 · VCV543069
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0245%, eas)
Conditions
1
TWIST1-related craniosynostosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.059 | GERP -1 |
| Overall | ||
| CADD | 3.699 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0245%
East Asian · 11/44,836 alleles
Filtering AF
0.0137%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.000684%
11/1,608,498 alleles · ultra-rare
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
- ERF
- Protein
- p.Ala415del
- Coding
- c.1243_1245del
- MANE Select
- NM_006494
- dbSNP
- rs759202471
- Type
- Deletion
- Location
- chr19:42248867 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.46 · 2 PDB
- Residue 415
- the 'disordered' region
Similar variants
- ERF p.Ala415Val Benign/Likely benign ★★ ⚠ same residue
- ERF p.Ala415= Likely benign ★ same residue
- ERF p.Arg143fs Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Asp188_Cys189insTer Pathogenic ★★ same condition
- ERF p.Gly299fs Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Lys401fs Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Pro358fs Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Ser304del 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/erf-p-ala415del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown