ESPN p.Pro724=
c.2172G>A · rs781377643 · VCV2077038
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.078 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.4 | GERP -2.7 |
| Overall | ||
| CADD | 2.047 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
Admixed American · 12/59,738 alleles
Filtering AF
0.0116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00902%
Overall
0.00279%
45/1,610,456 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0201% | 4,978 |
| African / African-American | 0.016% | 6,238 |
| South Asian | 0.00553% | 18,079 |
| European (non-Finnish) | 0.00136% | 73,670 |
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.Pro724=
- Coding
- c.2172G>A
- MANE Select
- NM_031475
- dbSNP
- rs781377643
- Type
- single nucleotide variant
- Location
- chr1:6451943 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
Similar variants
- ESPN p.Pro724Leu Uncertain significance ★ same residue
- ESPN p.Pro724Ser 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-pro724 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown