SON p.Asp2208=
c.6624T>C · rs374553176 · VCV2169988
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0449%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.095 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.6 | GERP -3.7 |
| Overall | ||
| CADD | 1.047 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0449%
European (non-Finnish) · 530/1,179,980 alleles
Filtering AF
0.0417%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0404%
Overall
0.0345%
557/1,613,910 alleles · ultra-rare
exomes 526/1,461,736 · genomes 31/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0449% | 2,226 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,840 |
| African / African-American | 0.00534% | 18,724 |
| Admixed American | 0.00167% | 59,954 |
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.Asp2208=
- Coding
- c.6624T>C
- MANE Select
- NM_138927
- dbSNP
- rs374553176
- Type
- single nucleotide variant
- Location
- chr21:33559742 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 2208
- 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-asp2208 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown