ESCO2 p.Ser323=
c.969C>A · rs1236225854 · VCV2919236
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000848%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP -1.5 |
| Overall | ||
| CADD | 3.617 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000848%
European (non-Finnish) · 10/1,179,440 alleles
Filtering AF
0.000429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.00062%
10/1,613,306 alleles · very rare
exomes 10/1,461,082 · genomes 0/152,224 · joint denominator
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
- ESCO2
- Protein
- p.Ser323=
- Coding
- c.969C>A
- MANE Select
- NM_001017420
- dbSNP
- rs1236225854
- Type
- single nucleotide variant
- Location
- chr8:27784013 (GRCh38)
- Gene constraint
- LOEUF 1.013 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 58.81
Similar variants
- ESCO2 c.1013+1G>A Likely pathogenic ★★ same type
- ESCO2 c.1131+1G>A Pathogenic ★★ same type
- ESCO2 c.1131+1G>T Pathogenic ★★ same type
- ESCO2 c.1132-7A>G Pathogenic/Likely pathogenic ★★ same type
- ESCO2 c.1353+1G>A Likely pathogenic ★★ same type
- ESCO2 c.1353+1G>T Likely pathogenic ★★ same type
- ESCO2 p.Arg169Ter Pathogenic ★★ same type
- ESCO2 p.Arg552Ter Pathogenic/Likely pathogenic ★★ 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/esco2-p-ser323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown