NSD2 p.Pro1300=
c.3900C>T · rs75949599 · VCV348448
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.35%, 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 0.27 | GERP -2.7, phastCons 0.98 |
| Overall | ||
| CADD | 7.686 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.35%
African / African-American · 2,516/75,050 alleles
Filtering AF
3.24%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.2%
Overall
0.18%
2,901/1,614,142 alleles · low-frequency
exomes 1,482/1,461,834 · genomes 1,419/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.35% | 30 |
| Admixed American | 0.237% | 423 |
| Remaining individualsnot grpmax-eligible | 0.21% | 477 |
| Middle Eastern | 0.115% | 866 |
| South Asian | 0.00878% | 11,384 |
| European (non-Finnish) | 0.00797% | 12,553 |
| Finnishnot grpmax-eligible | 0.00468% | 21,347 |
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.Pro1300=
- Coding
- c.3900C>T
- MANE Select
- NM_001042424
- dbSNP
- rs75949599
- Type
- single nucleotide variant
- Location
- chr4:1978711 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
- Residue 1300
- a β-strand; a UniProt-annotated variant site (in raust)
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-pro1300 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown