ESPN p.Arg791=
c.2373G>A · rs2522956116 · VCV3060303
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
ESPN-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.009 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.87 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 7.743 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,658 alleles
Overall
6.84e-05%
1/1,461,110 alleles · very rare
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.Arg791=
- Coding
- c.2373G>A
- MANE Select
- NM_031475
- dbSNP
- rs2522956116
- Type
- single nucleotide variant
- Location
- chr1:6457231 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 791
- a UniProt-annotated variant site (in ush1m; results in impaired elongation of microvilli and stereocilia consistent with a loss of function in parallel actin filament bundle assembly; retains localization to microvilli and stereocilia)
Disease context
ESPN-related disorder
Similar variants
- ESPN p.Arg791Gln Uncertain significance ★★ ⚠ same residue
- ESPN c.1464+1G>T Likely pathogenic ★ same condition
- ESPN c.2062-1G>T Likely pathogenic ★ same condition
- ESPN c.991-2A>G Likely pathogenic ★ same condition
- ESPN p.Gln447Ter Likely pathogenic ★ same condition
- ESPN p.Ser719Arg Likely pathogenic ★ same condition
- ESPN c.*4C>T Likely benign same condition
- ESPN p.Pro430= Likely benign same condition
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-arg791 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown