Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 36.3%, amr) — too common for a highly-penetrant pathogenic allele
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 -7.2 | GERP -2.6 |
| Overall | ||
| CADD | 0.113 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
36.3%
Admixed American · 16,576/45,724 alleles
Filtering AF
35.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 35.6%
Overall
25.3%
305,975/1,207,984 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 36.3% | 3 |
| Amishnot grpmax-eligible | 32.2% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 27.5% | 4 |
| European (non-Finnish) | 26.3% | 4 |
| Finnishnot grpmax-eligible | 26.1% | 4 |
| Remaining individualsnot grpmax-eligible | 25.8% | 4 |
| Middle Eastern | 25.7% | 4 |
| South Asian | 25.2% | 4 |
| East Asian | 13.1% | 8 |
| African / African-American | 6.91% | 14 |
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.Thr503=
- Coding
- c.1509G>A
- MANE Select
- NM_001421
- dbSNP
- rs2181440
- Type
- single nucleotide variant
- Location
- chrX:130067204 (GRCh38)
- Structure
- AlphaFold pLDDT 49.77
- Residue 503
- the 'disordered' region
Similar variants
- ELF4 p.Thr503Met Uncertain significance ★ ⚠ 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.Arg604Cys Benign ★★ same type
- ELF4 p.Ser369= 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-thr503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown