SOX18 p.Pro215=
c.645C>T · VCV4699922
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00154%, nfe)
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 -0.61 | GERP -3.2, phastCons 0.001 |
| Overall | ||
| CADD | 9.708 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00154%
European (non-Finnish) · 16/1,040,398 alleles
Filtering AF
0.00091%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000737%
Overall
0.00121%
16/1,317,890 alleles · very rare
exomes 16/1,166,000 · genomes 0/151,890 · 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
- SOX18
- Protein
- p.Pro215=
- Coding
- c.645C>T
- MANE Select
- NM_018419
- Type
- single nucleotide variant
- Location
- chr20:64048676 (GRCh38)
- Gene constraint
- LOEUF 1.483 · pLI 0.22 (gnomAD)
- Structure
- AlphaFold pLDDT 63.44
- Residue 215
- the 'disordered' region; the 'important for transcriptional activation' region
Similar variants
- SOX18 p.Gln161Ter Pathogenic/Likely pathogenic ★★ same type
- SOX18 p.Ala162Glu Uncertain significance ★★ ⚠ same type
- SOX18 p.Ala229Val Uncertain significance ★★ ⚠ same type
- SOX18 p.Ala250Thr Uncertain significance ★★ ⚠ same type
- SOX18 p.Ala30Ser Uncertain significance ★★ ⚠ same type
- SOX18 p.Arg140Leu Uncertain significance ★★ ⚠ same type
- SOX18 p.Arg271Lys Uncertain significance ★★ ⚠ same type
- SOX18 p.Asp13Asn 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/sox18-p-pro215 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown