SPEN p.Arg3552=
c.10656G>A · rs145784462 · VCV717467
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.711%, mid)
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 5.2 | GERP -0.61, phastCons 1 |
| Overall | ||
| CADD | 9.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.711%
Middle Eastern · 43/6,050 alleles
Filtering AF
0.542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.483%
Overall
0.11%
1,780/1,613,756 alleles · rare
exomes 1,632/1,461,418 · genomes 148/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.711% | 141 |
| South Asian | 0.329% | 304 |
| Remaining individualsnot grpmax-eligible | 0.186% | 539 |
| Ashkenazi Jewishnot grpmax-eligible | 0.132% | 758 |
| Admixed American | 0.129% | 777 |
| European (non-Finnish) | 0.1% | 996 |
| African / African-American | 0.0173% | 5,772 |
| Finnishnot grpmax-eligible | 0.00938% | 10,666 |
| East Asian | 0.00223% | 44,888 |
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.Arg3552=
- Coding
- c.10656G>A
- MANE Select
- NM_015001
- dbSNP
- rs145784462
- Type
- single nucleotide variant
- Location
- chr1:15937958 (GRCh38)
- Gene constraint
- LOEUF 0.094 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 3552
- a UniProt-annotated variant site (in ratars); a UniProt-annotated variant site (in ratars; uncertain significance); a β-strand; the spoc domain
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-arg3552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown