SON p.Ala46=
c.138G>A · rs536267719 · VCV2652605
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 2.4, phastCons 1 |
| Overall | ||
| CADD | 11.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,856 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00248%
40/1,613,618 alleles · ultra-rare
exomes 37/1,461,350 · genomes 3/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,476 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,498 |
| South Asian | 0.00659% | 15,171 |
| African / African-American | 0.00267% | 37,506 |
| European (non-Finnish) | 0.00178% | 56,174 |
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.Ala46=
- Coding
- c.138G>A
- MANE Select
- NM_138927
- dbSNP
- rs536267719
- Type
- single nucleotide variant
- Location
- chr21:33546273 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 46
- the 'disordered' region
Similar variants
- SON p.Ala46Glu Likely benign ★ 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
- SON c.6657+160A>C Uncertain significance ★★ 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-ala46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown