ERF p.Pro12=
c.36G>A · rs371076249 · VCV1487312
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00891%, 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 · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.7 | GERP -3.7 |
| Overall | ||
| CADD | 11.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,900 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.00186%
30/1,613,264 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,225 |
| African / African-American | 0.00401% | 24,967 |
| European (non-Finnish) | 0.00195% | 51,304 |
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.Pro12=
- Coding
- c.36G>A
- MANE Select
- NM_006494
- dbSNP
- rs371076249
- Type
- single nucleotide variant
- Location
- chr19:42250552 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.46 · 2 PDB
Similar variants
- ERF p.Pro12Leu Uncertain significance ★ ⚠ same residue
- ERF p.Arg183Ter Pathogenic ★★ same condition
- ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Ser24Ter Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Arg458Gly Uncertain significance ★★ ⚠ same condition
- ERF p.Arg493His Uncertain significance ★★ ⚠ 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-pro12 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown