SON p.Arg2416fs
c.7248del · rs34373121 · VCV1333147
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 5.3, phastCons 1 |
| Overall | ||
| CADD | 31.0 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | chr1:157710152 segmental duplication, simple repeat · ambiguous alignment · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 100% | 1 |
| Amishnot grpmax-eligible | 100% | 1 |
| East Asiangrpmax | 100% | 1 |
| Admixed American | 100% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 100% | 1 |
| South Asian | 100% | 1 |
| African / African-American | 100% | 1 |
| Remaining individualsnot grpmax-eligible | 100% | 1 |
| European (non-Finnish) | 100% | 1 |
| Middle Eastern | 100% | 1 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Arg2416fs
- Coding
- c.7248del
- MANE Select
- NM_138927
- dbSNP
- rs34373121
- Type
- Deletion
- Location
- chr21:33576391 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 2416
- the drbm domain
Similar variants
- SON p.Arg1906fs Pathogenic ★★ same condition
- SON p.Lys128fs Pathogenic ★★ same condition
- SON p.Lys1888fs Pathogenic/Likely pathogenic ★★ same condition
- SON p.Met1284fs Pathogenic/Likely pathogenic ★★ same condition
- SON p.Thr1633fs Pathogenic/Likely pathogenic ★★ same condition
- SON p.Val1918fs Pathogenic/Likely pathogenic ★★ same condition
- SON p.729NTMDSQMLAS[2] Uncertain significance ★★ same condition
- SON c.6321+1del Pathogenic ★ same condition
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-arg2416fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown