ELF4 p.Arg604His
c.1811G>A · VCV4017476
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0603 | likely benign |
|---|---|---|
| REVEL | 0.036 | moderately benign-leaning |
| SaProt | LLR -6.48 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.51 | GERP 1.4, phastCons 0.067 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 2,786 bp · p 0.57 · regional, not allelic |
| Overall | ||
| CADD | 15.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0126% | 7,938 |
| European (non-Finnish)grpmax | 0.00882% | 11,332 |
| South Asian | 0.00879% | 11,371 |
| Admixed American | 0.00436% | 22,924 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- ELF4
- Protein
- p.Arg604His
- Coding
- c.1811G>A
- MANE Select
- NM_001421
- Type
- single nucleotide variant
- Location
- chrX:130066902 (GRCh38)
- Structure
- AlphaFold pLDDT 49.77
- Residue 604
- a UniProt-annotated variant site (no effect on transcriptional activity shown in ifnb1 promoter-driven luciferase assay); the 'disordered' region
Similar variants
- ELF4 p.Arg604Cys Benign ★★ same residue
- ELF4 p.Gly206Asp Uncertain significance ★★ ⚠ same type
- ELF4 p.Ser413Leu Uncertain significance ★★ ⚠ same type
- ELF4 p.Ala147Val Benign/Likely benign ★★ same type
- ELF4 p.Ser369= Benign ★★ same type
- ELF4 p.Thr503= Benign ★★ same type
- ELF4 p.Arg185Ter Likely pathogenic ★ same type
- ELF4 p.Arg234Ter 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/elf4-p-arg604his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown