EPS8L2 p.Arg613=
c.1839C>T · VCV4804444
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0991%, mid)
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 0.007 | GERP -0.92, phastCons 0.85 |
| Overall | ||
| CADD | 10.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0991%
Middle Eastern · 6/6,054 alleles
Filtering AF
0.0432%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0295%
Overall
0.00646%
104/1,609,498 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0991% | 1,009 |
| South Asian | 0.0121% | 8,231 |
| European (non-Finnish) | 0.00696% | 14,375 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,770 |
| Admixed American | 0.00168% | 59,696 |
| African / African-American | 0.00133% | 74,968 |
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
- EPS8L2
- Protein
- p.Arg613=
- Coding
- c.1839C>T
- MANE Select
- NM_022772
- Type
- single nucleotide variant
- Location
- chr11:726389 (GRCh38)
- Gene constraint
- LOEUF 1.164 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 2 PDB
Similar variants
- EPS8L2 p.Glu165Ter Likely pathogenic ★★ same type
- EPS8L2 p.Arg102Trp Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg193Gln Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg245Gln Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg272Trp Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg365Cys Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg506Leu Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg76Trp Uncertain significance ★★ ⚠ 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/eps8l2-p-arg613 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown