ESPN p.Leu531=
c.1593G>A · rs577834330 · VCV731668
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.17%, 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 4.6 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 11.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.17%
African / African-American · 115/67,734 alleles
Filtering AF
0.145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.135%
Overall
0.00876%
127/1,450,198 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.17% | 589 |
| Middle Eastern | 0.0243% | 4,112 |
| Admixed American | 0.0101% | 9,922 |
| Remaining individualsnot grpmax-eligible | 0.00898% | 11,138 |
| European (non-Finnish) | 0.000181% | 552,837 |
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.Leu531=
- Coding
- c.1593G>A
- MANE Select
- NM_031475
- dbSNP
- rs577834330
- Type
- single nucleotide variant
- Location
- chr1:6448769 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 531
- the 'disordered' region
Similar variants
- 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
- ESPN p.Ala729Glu 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-leu531 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown