FES p.Ala588=
c.1764G>A · rs62640875 · VCV790155
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.05%, 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 -20 | GERP -3.6 |
| Overall | ||
| CADD | 0.072 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.05%
African / African-American · 2,289/75,028 alleles
Filtering AF
2.95%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.9%
Overall
0.165%
2,658/1,613,708 alleles · low-frequency
exomes 1,325/1,461,414 · genomes 1,333/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.05% | 33 |
| Admixed American | 0.25% | 400 |
| Remaining individualsnot grpmax-eligible | 0.221% | 453 |
| Middle Eastern | 0.0503% | 1,989 |
| East Asian | 0.0178% | 5,610 |
| European (non-Finnish) | 0.00551% | 18,153 |
| South Asian | 0.00549% | 18,214 |
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
- FES
- Protein
- p.Ala588=
- Coding
- c.1764G>A
- MANE Select
- NM_002005
- dbSNP
- rs62640875
- Type
- single nucleotide variant
- Location
- chr15:90892763 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.63 · 12 PDB
- Residue 588
- the protein kinase domain; a β-strand
Similar variants
- FES p.Leu459= Benign ★★ same type
- FES p.Met323Val Benign ★★ same type
- FES p.Ala192Pro Uncertain significance ★ ⚠ same type
- FES p.Ala22Asp Uncertain significance ★ ⚠ same type
- FES p.Ala243Val Uncertain significance ★ ⚠ same type
- FES p.Ala370Val Uncertain significance ★ ⚠ same type
- FES p.Ala45Pro Uncertain significance ★ ⚠ same type
- FES p.Ala548Pro 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/fes-p-ala588 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown