ERF p.Ser368=
c.1104T>C · rs76105803 · VCV476623
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 10.4%, afr) — too common for a highly-penetrant pathogenic allele
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 -1.1 | GERP -2 |
| Overall | ||
| CADD | 4.244 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.4%
African / African-American · 7,775/74,978 alleles
Filtering AF
10.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.1%
Overall
0.599%
9,641/1,609,782 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.4% | 10 |
| Admixed American | 0.882% | 113 |
| Remaining individualsnot grpmax-eligible | 0.726% | 138 |
| Middle Eastern | 0.429% | 233 |
| Ashkenazi Jewishnot grpmax-eligible | 0.108% | 924 |
| European (non-Finnish) | 0.0679% | 1,473 |
| South Asian | 0.022% | 4,550 |
| East Asian | 0.0134% | 7,470 |
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.Ser368=
- Coding
- c.1104T>C
- MANE Select
- NM_006494
- dbSNP
- rs76105803
- Type
- single nucleotide variant
- Location
- chr19:42249008 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.46 · 2 PDB
- Residue 368
- the 'disordered' region
Similar variants
- 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
- ERF p.Lys401Glu 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-ser368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown