ESPN p.Pro432=
c.1296A>C · rs765268659 · VCV770108
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 10.1%, 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 -9.1 | GERP -2.9 |
| Overall | ||
| CADD | 0.294 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.1%
East Asian · 770/7,656 alleles
Filtering AF
9.47%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.23%
Overall
3.8%
16,340/430,408 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 10.1% | 10 |
| African / African-American | 6.96% | 14 |
| Amishnot grpmax-eligible | 4.9% | 20 |
| Finnishnot grpmax-eligible | 4.9% | 20 |
| Admixed American | 4.56% | 22 |
| Remaining individualsnot grpmax-eligible | 4.24% | 24 |
| Middle Eastern | 4.13% | 24 |
| Ashkenazi Jewishnot grpmax-eligible | 3.89% | 26 |
| South Asian | 3.6% | 28 |
| European (non-Finnish) | 3.29% | 30 |
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.Pro432=
- Coding
- c.1296A>C
- MANE Select
- NM_031475
- dbSNP
- rs765268659
- Type
- single nucleotide variant
- Location
- chr1:6445767 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 432
- 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-pro432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown