ERF p.Glu35Ter
c.103G>T · VCV4082546
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Common craniosynostosis syndromes
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 4 |
| Splicing | ||
| SpliceAI | Δ0.90 | acceptor gain · deltas |
| Pangolin | Δ0.68 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 54.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ERF
- Protein
- p.Glu35Ter
- Coding
- c.103G>T
- MANE Select
- NM_006494
- Type
- single nucleotide variant
- Location
- chr19:42250485 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 55.46 · 2 PDB
- Residue 35
- a DNA-binding region; an α-helix
Disease context
Common craniosynostosis syndromes
Similar variants
- ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Arg233Ter Pathogenic ★★ same condition
- ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same condition
- ERF p.Gly53Arg Likely pathogenic ★★ same condition
- ERF p.Tyr89Cys Pathogenic ★★ same condition
- ERF p.Met1Leu Likely pathogenic ★ same condition
- ERF p.Ser169Ter 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-glu35ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown