ESPL1 p.Ser1239Ter
c.3716C>A · rs2498523765 · VCV2632231
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ESPL1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 18 of 31 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP -0.36, phastCons 0.21 |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ESPL1
- Protein
- p.Ser1239Ter
- Coding
- c.3716C>A
- MANE Select
- NM_012291
- dbSNP
- rs2498523765
- Type
- single nucleotide variant
- Location
- chr12:53286452 (GRCh38)
- Gene constraint
- LOEUF 0.292 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.67 · 9 PDB
Disease context
ESPL1-related disorder
Similar variants
- ESPL1 c.6161+7C>T Likely benign same condition
- ESPL1 p.Ala116Val Benign ⚠ same condition
- ESPL1 p.Ala1438= Likely benign same condition
- ESPL1 p.Arg1318Gln Likely benign same condition
- ESPL1 p.Asn1723= Likely benign same condition
- ESPL1 p.Asp1351= Likely benign same condition
- ESPL1 p.Gly1510Arg Likely benign same condition
- ESPL1 p.His1078Asn 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/espl1-p-ser1239ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown