SON p.Asp842=
c.2526T>C · rs536378135 · VCV2697432
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0627%, sas)
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 -0.47 | GERP -2.3, phastCons 0.057 |
| Overall | ||
| CADD | 3.211 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0627%
South Asian · 56/89,260 alleles
Filtering AF
0.0496%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0448%
Overall
0.00751%
118/1,571,252 alleles · ultra-rare
exomes 60/1,459,442 · genomes 58/111,810 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0627% | 1,594 |
| African / African-American | 0.0385% | 2,594 |
| Admixed American | 0.0141% | 7,088 |
| East Asian | 0.0116% | 8,655 |
| Finnishnot grpmax-eligible | 0.00821% | 12,186 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00347% | 28,782 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,922 |
| European (non-Finnish) | 0.00146% | 68,392 |
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.Asp842=
- Coding
- c.2526T>C
- MANE Select
- NM_138927
- dbSNP
- rs536378135
- Type
- single nucleotide variant
- Location
- chr21:33551757 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 842
- the '17 x 10 aa tandem repeats of l-a-[st]-[nsg]-[ts]-mdsqm' 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-asp842 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown