NSD2 p.Arg546=
c.1638G>A · rs571693539 · VCV1680173
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0417%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP -0.4, phastCons 1 |
| Overall | ||
| CADD | 8.968 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0417%
Admixed American · 25/59,968 alleles
Filtering AF
0.0289%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0248%
Overall
0.00236%
38/1,613,456 alleles · ultra-rare
exomes 18/1,461,224 · genomes 20/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0417% | 2,399 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,940 |
| African / African-American | 0.00533% | 18,749 |
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
- NSD2
- Protein
- p.Arg546=
- Coding
- c.1638G>A
- MANE Select
- NM_001042424
- dbSNP
- rs571693539
- Type
- single nucleotide variant
- Location
- chr4:1935226 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
- Residue 546
- the 'disordered' region
Similar variants
- NSD2 p.Arg450Ter Likely pathogenic ★★ same type
- NSD2 p.Arg755Ter Pathogenic/Likely pathogenic ★★ same type
- NSD2 p.Arg935Ter Pathogenic ★★ same type
- NSD2 p.Pro895Leu Pathogenic ★★ same type
- NSD2 p.Ala320Thr Uncertain significance ★★ ⚠ same type
- NSD2 p.Ala383Gly Uncertain significance ★★ ⚠ same type
- NSD2 p.Ala693Asp Uncertain significance ★★ ⚠ same type
- NSD2 p.Ala965Thr 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/nsd2-p-arg546 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown