NSD2 p.Pro72=
c.216C>G · rs112939388 · VCV348421
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.01%, afr)
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 -0.9 | GERP -0.66, phastCons 0.002 |
| Overall | ||
| CADD | 6.579 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.01%
African / African-American · 1,508/75,006 alleles
Filtering AF
1.93%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.89%
Overall
0.109%
1,757/1,613,316 alleles · low-frequency
exomes 872/1,461,016 · genomes 885/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.01% | 50 |
| Remaining individualsnot grpmax-eligible | 0.133% | 753 |
| Admixed American | 0.132% | 759 |
| Middle Eastern | 0.066% | 1,514 |
| European (non-Finnish) | 0.00678% | 14,743 |
| South Asian | 0.0033% | 30,342 |
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.Pro72=
- Coding
- c.216C>G
- MANE Select
- NM_001042424
- dbSNP
- rs112939388
- Type
- single nucleotide variant
- Location
- chr4:1900870 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
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-pro72 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown