SON p.Cys92=
c.276C>T · rs1457885419 · VCV1902660
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00677%, 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 1.2 | GERP -0.2, phastCons 1 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00677%
East Asian · 3/44,282 alleles
Filtering AF
0.0018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000898%
Overall
0.000905%
14/1,547,640 alleles · very rare
exomes 13/1,395,878 · genomes 1/151,762 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00677% | 14,761 |
| Remaining individualsnot grpmax-eligible | 0.00168% | 59,548 |
| African / African-American | 0.00139% | 71,774 |
| European (non-Finnish) | 0.000779% | 128,389 |
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.Cys92=
- Coding
- c.276C>T
- MANE Select
- NM_138927
- dbSNP
- rs1457885419
- Type
- single nucleotide variant
- Location
- chr21:33549507 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 92
- the 'disordered' region
Similar variants
- 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
- SON c.6657+316G>A 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-cys92 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown