NSD2 p.Pro1342=
c.4026C>G · rs147624398 · VCV348450
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.089%, 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 -5.7 | GERP -2.9 |
| Overall | ||
| CADD | 0.017 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.089%
Admixed American · 53/59,534 alleles
Filtering AF
0.0699%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.063%
Overall
0.0244%
391/1,603,668 alleles · ultra-rare
exomes 360/1,451,328 · genomes 31/152,340 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.089% | 1,123 |
| South Asian | 0.0819% | 1,220 |
| Remaining individualsnot grpmax-eligible | 0.0387% | 2,582 |
| East Asian | 0.036% | 2,781 |
| European (non-Finnish) | 0.0184% | 5,428 |
| African / African-American | 0.0107% | 9,362 |
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.Pro1342=
- Coding
- c.4026C>G
- MANE Select
- NM_001042424
- dbSNP
- rs147624398
- Type
- single nucleotide variant
- Location
- chr4:1978837 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
- Residue 1342
- the 'disordered' region; a UniProt-annotated variant site (in raust)
Similar variants
- NSD2 p.Pro1342Arg Uncertain significance ★ ⚠ same residue
- NSD2 p.Pro1342Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- NSD2 p.Pro1342Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- NSD2 p.Pro1342His Likely benign ★ same residue
- 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
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-pro1342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown