EPS8L2 p.Ser404=
c.1212C>T · VCV3620722
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00332%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.74 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.8 | GERP -2.9 |
| Overall | ||
| CADD | 1.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00332%
South Asian · 3/90,258 alleles
Filtering AF
0.000883%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000445%
Overall
0.000249%
4/1,606,978 alleles · very rare
exomes 4/1,454,924 · genomes 0/152,054 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00332% | 30,086 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,106 |
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.Ser404=
- Coding
- c.1212C>T
- MANE Select
- NM_022772
- Type
- single nucleotide variant
- Location
- chr11:722676 (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-ser404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown