SON p.Pro540=
c.1620T>G · rs752160227 · VCV2178005
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, nfe)
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 -0.075 | GERP -2.2, phastCons 0.81 |
| Overall | ||
| CADD | 6.376 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
European (non-Finnish) · 195/1,179,492 alleles
Filtering AF
0.0146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0139%
Overall
0.0124%
200/1,613,256 alleles · ultra-rare
exomes 197/1,461,260 · genomes 3/151,996 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0165% | 6,049 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,817 |
| East Asian | 0.00223% | 44,806 |
| African / African-American | 0.00134% | 74,842 |
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.Pro540=
- Coding
- c.1620T>G
- MANE Select
- NM_138927
- dbSNP
- rs752160227
- Type
- single nucleotide variant
- Location
- chr21:33550851 (GRCh38)
- Gene constraint
- LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.48 · 4 PDB
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-pro540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown