ESPN p.Pro431=
c.1293A>C · rs530882053 · VCV769235
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 11.4%, eas) — too common for a highly-penetrant pathogenic allele
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 -6.8 | GERP -1.8 |
| Overall | ||
| CADD | 2.627 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.4%
East Asian · 921/8,058 alleles
Filtering AF
10.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.6%
Overall
4.69%
18,202/388,376 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 11.4% | 9 |
| African / African-American | 8.72% | 11 |
| Amishnot grpmax-eligible | 7.77% | 13 |
| Admixed American | 6.33% | 16 |
| Remaining individualsnot grpmax-eligible | 5.23% | 19 |
| Finnishnot grpmax-eligible | 5.2% | 19 |
| Middle Eastern | 4.92% | 20 |
| Ashkenazi Jewishnot grpmax-eligible | 4.82% | 21 |
| European (non-Finnish) | 4.17% | 24 |
| South Asian | 3.04% | 33 |
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.Pro431=
- Coding
- c.1293A>C
- MANE Select
- NM_031475
- dbSNP
- rs530882053
- Type
- single nucleotide variant
- Location
- chr1:6445764 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 431
- the 'disordered' region
Similar variants
- ESPN p.Pro431Ala Uncertain significance ★★ ⚠ same residue
- ESPN p.Pro431fs Uncertain significance ★ 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
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-pro431 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown