SPEN p.Arg206=
c.618C>T · VCV4083813
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.459%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 13.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.459%
Admixed American · 275/59,976 alleles
Filtering AF
0.414%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.397%
Overall
0.0367%
593/1,613,974 alleles · rare
exomes 538/1,461,872 · genomes 55/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.459% | 218 |
| Finnishnot grpmax-eligible | 0.141% | 711 |
| Remaining individualsnot grpmax-eligible | 0.0528% | 1,894 |
| European (non-Finnish) | 0.0164% | 6,082 |
| African / African-American | 0.00133% | 75,002 |
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
- SPEN
- Protein
- p.Arg206=
- Coding
- c.618C>T
- MANE Select
- NM_015001
- Type
- single nucleotide variant
- Location
- chr1:15876415 (GRCh38)
- Gene constraint
- LOEUF 0.094 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 206
- the 'disordered' region; a DNA-binding region
Similar variants
- SPEN p.Arg1170Ter Pathogenic ★★ same type
- SPEN p.Arg1241Ter Pathogenic ★★ same type
- SPEN p.Arg1265Ter Pathogenic ★★ same type
- SPEN p.Arg2337Ter Likely pathogenic ★★ same type
- SPEN p.Arg2342Ter Pathogenic ★★ same type
- SPEN p.Arg308Ter Pathogenic ★★ same type
- SPEN p.Arg3168Ter Pathogenic/Likely pathogenic ★★ same type
- SPEN p.Arg535Ter 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/spen-p-arg206 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown