ESPN p.Pro707=
c.2121G>A · rs376431619 · VCV752688
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.012 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -2.7 |
| Overall | ||
| CADD | 2.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,020 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00395%
Overall
0.0018%
29/1,610,482 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,020 |
| East Asian | 0.0134% | 7,464 |
| Admixed American | 0.01% | 9,956 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,468 |
| African / African-American | 0.00801% | 12,478 |
| South Asian | 0.00111% | 90,492 |
| European (non-Finnish) | 0.000339% | 294,677 |
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.Pro707=
- Coding
- c.2121G>A
- MANE Select
- NM_031475
- dbSNP
- rs376431619
- Type
- single nucleotide variant
- Location
- chr1:6451892 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 707
- the 'disordered' region
Similar variants
- ESPN p.Pro707Leu 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
- 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-pro707 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown