ESPL1 p.Ser969=
c.2907G>A · rs115860198 · VCV781074
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.31%, afr)
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 -5 | GERP -3.9 |
| Overall | ||
| CADD | 0.236 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.31%
African / African-American · 3,233/75,050 alleles
Filtering AF
4.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.13%
Overall
0.235%
3,798/1,614,186 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.31% | 23 |
| Admixed American | 0.365% | 274 |
| Remaining individualsnot grpmax-eligible | 0.32% | 313 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.0165% | 6,072 |
| European (non-Finnish) | 0.0107% | 9,365 |
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
- ESPL1
- Protein
- p.Ser969=
- Coding
- c.2907G>A
- MANE Select
- NM_012291
- dbSNP
- rs115860198
- Type
- single nucleotide variant
- Location
- chr12:53283244 (GRCh38)
- Gene constraint
- LOEUF 0.292 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.67 · 9 PDB
Similar variants
- ESPL1 c.6162-10C>T Benign ★★ same type
- ESPL1 p.Ala1462Thr Benign ★★ same type
- ESPL1 p.Asn918Ser Benign ★★ same type
- ESPL1 p.Gly1337Val Benign ★★ same type
- ESPL1 p.Ile1488Asn Benign ★★ same type
- ESPL1 p.Thr2073Met Likely benign ★★ ⚠ same type
- ESPL1 c.5241+1G>A Uncertain significance ★ same type
- ESPL1 p.Ala1110Ser 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/espl1-p-ser969 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown