SON p.Arg1990=
c.5970T>C · rs528498338 · VCV790893
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.111%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type. | ||
| REVEL | 0.053 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Overall | ||
| CADD | 0.084 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.111%
Admixed American · 62/56,096 alleles
Filtering AF
0.0884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0805%
Overall
0.0146%
229/1,565,592 alleles · rare
exomes 134/1,425,836 · genomes 95/139,756 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.111% | 905 |
| South Asian | 0.0274% | 3,654 |
| East Asian | 0.0243% | 4,116 |
| European (non-Finnish) | 0.0107% | 9,356 |
| African / African-American | 0.0073% | 13,692 |
| Remaining individualsnot grpmax-eligible | 0.00494% | 20,263 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0035% | 28,598 |
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
- SON
- Protein
- p.Arg1990=
- Coding
- c.5970T>C
- MANE Select
- NM_138927
- dbSNP
- rs528498338
- Type
- single nucleotide variant
- Location
- chr21:33555201 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 1990
- the 'disordered' region; the '7 x 7 aa repeats of p-s-r-r-s-r-[ts]' region; the '2 x 19 aa repeats of p-s-r-r-r-r-s-r-s-v-v-r-r-r-s-f-s-i-s' region
Similar variants
- SON p.Arg1990His Uncertain significance ★★ ⚠ same residue
- SON p.Arg1990Cys Uncertain significance ★ ⚠ same residue
- SON c.6321+1G>A Pathogenic ★★ same type
- SON p.Arg1081Ter Pathogenic ★★ same type
- SON p.Arg1112Ter Pathogenic ★★ same type
- SON p.Arg1825Ter Pathogenic ★★ same type
- SON p.Arg2008Ter Pathogenic ★★ same type
- SON p.Gln96Ter Pathogenic/Likely 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/son-p-arg1990 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown