ESPN p.Pro350=
c.1050G>A · VCV4930081
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00988%, sas)
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 -14 | GERP -2.4 |
| Overall | ||
| CADD | 0.195 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00988%
South Asian · 9/91,086 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00105%
17/1,614,204 alleles · very rare
exomes 14/1,461,880 · genomes 3/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00988% | 10,121 |
| Admixed American | 0.00333% | 30,013 |
| African / African-American | 0.00266% | 37,526 |
| East Asian | 0.00223% | 44,884 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
| European (non-Finnish) | 0.000169% | 590,012 |
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.Pro350=
- Coding
- c.1050G>A
- MANE Select
- NM_031475
- Type
- single nucleotide variant
- Location
- chr1:6444540 (GRCh38)
- Gene constraint
- LOEUF 1.307 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76
- Residue 350
- the 'disordered' region
Similar variants
- ESPN p.Pro350Ser Benign/Likely benign ★★ same residue
- ESPN p.Pro350Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
- ESPN p.Pro350Leu 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
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-pro350 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown