Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 25.4%, afr) — 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 -1.1 | GERP -3.3, phastCons 0.001 |
| Overall | ||
| CADD | 8.096 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.4%
African / African-American · 19,004/74,846 alleles
Filtering AF
25.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 25%
Overall
13.5%
216,905/1,606,166 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 25.4% | 4 |
| Amishnot grpmax-eligible | 19.3% | 5 |
| Middle Eastern | 19% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 17.9% | 6 |
| East Asian | 17.5% | 6 |
| South Asian | 16.1% | 6 |
| Remaining individualsnot grpmax-eligible | 14.2% | 7 |
| European (non-Finnish) | 12.5% | 8 |
| Finnishnot grpmax-eligible | 12.4% | 8 |
| Admixed American | 9.62% | 10 |
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.Arg303=
- Coding
- c.909C>G
- MANE Select
- NM_031475
- dbSNP
- rs2311045
- Type
- single nucleotide variant
- Location
- chr1:6440984 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
Similar variants
- ESPN p.Arg303His Uncertain significance ★ ⚠ same residue
- ESPN p.Arg303Ser 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-arg303 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown