SPEN p.Arg535=
c.1605A>C · rs61756185 · VCV2578563
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.545%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.024 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.76 | GERP -3.8, phastCons 0.96 |
| Overall | ||
| CADD | 8.626 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.545%
South Asian · 486/89,240 alleles
Filtering AF
0.505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.489%
Overall
0.423%
6,784/1,605,162 alleles · rare
exomes 6,271/1,452,886 · genomes 513/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.545% | 184 |
| European (non-Finnish) | 0.496% | 202 |
| Remaining individualsnot grpmax-eligible | 0.311% | 321 |
| Admixed American | 0.211% | 475 |
| Middle Eastern | 0.199% | 504 |
| Finnishnot grpmax-eligible | 0.0891% | 1,122 |
| African / African-American | 0.0843% | 1,186 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0237% | 4,211 |
| East Asian | 0.0158% | 6,318 |
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.Arg535=
- Coding
- c.1605A>C
- MANE Select
- NM_015001
- dbSNP
- rs61756185
- Type
- single nucleotide variant
- Location
- chr1:15919487 (GRCh38)
- Gene constraint
- LOEUF 0.094 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 535
- a UniProt-annotated variant site (in ratars); an α-helix; the rrm 4 domain; a DNA-binding region
Similar variants
- SPEN p.Arg535Ter Pathogenic ★★ same residue
- SPEN p.Arg535Gln Uncertain significance ★ same residue
- 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
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-arg535 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown