SON p.Leu2391=
c.7173A>G · rs144018038 · VCV2652627
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.446%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.108 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.27 | GERP -1.6, phastCons 0.12 |
| Overall | ||
| CADD | 3.361 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.446%
Middle Eastern · 27/6,050 alleles
Filtering AF
0.315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.271%
Overall
0.0241%
388/1,611,938 alleles · rare
exomes 356/1,459,600 · genomes 32/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.446% | 224 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0947% | 1,056 |
| South Asian | 0.0582% | 1,718 |
| Remaining individualsnot grpmax-eligible | 0.0529% | 1,891 |
| Admixed American | 0.03% | 3,334 |
| European (non-Finnish) | 0.0187% | 5,355 |
| African / African-American | 0.0107% | 9,376 |
| Finnishnot grpmax-eligible | 0.00156% | 64,026 |
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.Leu2391=
- Coding
- c.7173A>G
- MANE Select
- NM_138927
- dbSNP
- rs144018038
- Type
- single nucleotide variant
- Location
- chr21:33575845 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
- Residue 2391
- the drbm domain
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-leu2391 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown