EPS8L2 p.Pro205=
c.615G>C · rs1004247653 · VCV1616110
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0124%, afr)
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 -10 | GERP -1.9 |
| Overall | ||
| CADD | 0.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0124%
African / African-American · 9/72,866 alleles
Filtering AF
0.00639%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00479%
Overall
0.000912%
14/1,534,742 alleles · ultra-rare
exomes 6/1,382,580 · genomes 8/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0124% | 8,096 |
| Admixed American | 0.004% | 25,013 |
| Remaining individualsnot grpmax-eligible | 0.00336% | 29,783 |
| European (non-Finnish) | 8.75e-05% | 1,143,000 |
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.Pro205=
- Coding
- c.615G>C
- MANE Select
- NM_022772
- dbSNP
- rs1004247653
- Type
- single nucleotide variant
- Location
- chr11:721121 (GRCh38)
- Gene constraint
- LOEUF 1.164 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 2 PDB
- Residue 205
- the 'disordered' region
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-pro205 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown