ESPN p.Ala133=
c.399G>A · VCV4927930
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 0.95 | GERP -2.4, phastCons 0.001 |
| Overall | ||
| CADD | 8.145 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,048 alleles
Filtering AF
0.00291%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0026%
Overall
0.00316%
51/1,612,970 alleles · ultra-rare
exomes 44/1,460,702 · genomes 7/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,048 |
| European (non-Finnish) | 0.00381% | 26,221 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| African / African-American | 0.00267% | 37,516 |
| East Asian | 0.00223% | 44,864 |
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
- ESPN
- Protein
- p.Ala133=
- Coding
- c.399G>A
- MANE Select
- NM_031475
- Type
- single nucleotide variant
- Location
- chr1:6428330 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
Similar variants
- ESPN p.Ala133Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- ESPN c.1464+1G>A Likely pathogenic ★★ same type
- ESPN p.Ala139Thr Uncertain significance ★★ ⚠ same type
- ESPN p.Ala23Thr Uncertain significance ★★ ⚠ same type
- ESPN p.Ala484Thr Uncertain significance ★★ ⚠ same type
- ESPN p.Ala591Val Uncertain significance ★★ ⚠ same type
- ESPN p.Ala610Pro Uncertain significance ★★ ⚠ same type
- ESPN p.Ala624Thr 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/espn-p-ala133 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown