EPS8 p.Gln691=
c.2073A>G · rs61729666 · VCV513633
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.83%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.106 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.32 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 0.55 | GERP 0.053, phastCons 1 |
| Overall | ||
| CADD | 6.782 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.83%
African / African-American · 2,835/74,112 alleles
Filtering AF
3.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.66%
Overall
0.198%
3,123/1,577,730 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.83% | 26 |
| Admixed American | 0.232% | 431 |
| Remaining individualsnot grpmax-eligible | 0.217% | 462 |
| Middle Eastern | 0.017% | 5,880 |
| South Asian | 0.00812% | 12,319 |
| European (non-Finnish) | 0.00147% | 68,116 |
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
- EPS8
- Protein
- p.Gln691=
- Coding
- c.2073A>G
- MANE Select
- NM_004447
- dbSNP
- rs61729666
- Type
- single nucleotide variant
- Location
- chr12:15624379 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 70.77 · 2 PDB
- Residue 691
- the 'effector region' region; the 'amphipathic helix' region
Similar variants
- EPS8 c.205-8A>G Uncertain significance ★★ same type
- EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same type
- EPS8 p.Ala219Val Uncertain significance ★★ ⚠ same type
- EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg432Gln Uncertain significance ★★ ⚠ same type
- EPS8 p.Arg434Cys 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/eps8-p-gln691 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown