EPS8L2 p.Arg245=
c.735G>A · rs1012881286 · VCV1604478
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0118%, amr)
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 0.37 | GERP -1.3, phastCons 0.99 |
| Overall | ||
| CADD | 8.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0118%
Admixed American · 6/50,912 alleles
Filtering AF
0.00512%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00423%
Overall
0.00481%
74/1,539,836 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0118% | 8,485 |
| European (non-Finnish) | 0.00576% | 17,374 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,836 |
| African / African-American | 0.00137% | 72,938 |
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.Arg245=
- Coding
- c.735G>A
- MANE Select
- NM_022772
- dbSNP
- rs1012881286
- Type
- single nucleotide variant
- Location
- chr11:721319 (GRCh38)
- Gene constraint
- LOEUF 1.164 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 2 PDB
Similar variants
- EPS8L2 p.Arg245Gln Uncertain significance ★★ ⚠ same residue
- EPS8L2 p.Glu165Ter Likely pathogenic ★★ same type
- EPS8L2 p.Arg102Trp Uncertain significance ★★ ⚠ same type
- EPS8L2 p.Arg193Gln 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-arg245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown