SPEN p.Pro3495=
c.10485C>T · rs57175033 · VCV786982
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.92%, 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 -3.5 | GERP -4.8 |
| Overall | ||
| CADD | 1.875 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.92%
African / African-American · 2,189/75,028 alleles
Filtering AF
2.82%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.77%
Overall
0.154%
2,486/1,613,604 alleles · low-frequency
exomes 1,147/1,461,304 · genomes 1,339/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.92% | 34 |
| Remaining individualsnot grpmax-eligible | 0.208% | 481 |
| Admixed American | 0.193% | 517 |
| Middle Eastern | 0.099% | 1,010 |
| East Asian | 0.00669% | 14,956 |
| European (non-Finnish) | 0.00331% | 30,244 |
| South Asian | 0.00329% | 30,363 |
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.Pro3495=
- Coding
- c.10485C>T
- MANE Select
- NM_015001
- dbSNP
- rs57175033
- Type
- single nucleotide variant
- Location
- chr1:15937621 (GRCh38)
- Gene constraint
- LOEUF 0.094 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 3495
- a UniProt-annotated variant site (in ratars); a UniProt-annotated variant site (in ratars; uncertain significance)
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-pro3495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown