EPS8L2 p.Ala172=
c.516C>G · VCV3631114
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0766%, 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 -5.1 | GERP -2.3 |
| Overall | ||
| CADD | 8.154 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0766%
African / African-American · 50/65,302 alleles
Filtering AF
0.0596%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0536%
Overall
0.00405%
59/1,455,216 alleles · ultra-rare
exomes 22/1,326,710 · genomes 37/128,506 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0766% | 1,306 |
| Remaining individualsnot grpmax-eligible | 0.00542% | 18,449 |
| Admixed American | 0.00214% | 46,838 |
| European (non-Finnish) | 0.000457% | 218,617 |
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.Ala172=
- Coding
- c.516C>G
- MANE Select
- NM_022772
- Type
- single nucleotide variant
- Location
- chr11:720868 (GRCh38)
- Gene constraint
- LOEUF 1.164 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.67 · 2 PDB
- Residue 172
- the pid domain
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-ala172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown