NSD2 p.Glu339=
c.1017G>A · rs375995389 · VCV1899052
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, 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 0.068 | GERP -3.1, phastCons 0.59 |
| Overall | ||
| CADD | 5.833 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
African / African-American · 13/74,938 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00813%
Overall
0.000991%
16/1,613,760 alleles · ultra-rare
exomes 7/1,461,820 · genomes 9/151,940 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0173% | 5,764 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| European (non-Finnish) | 8.47e-05% | 1,179,998 |
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.Glu339=
- Coding
- c.1017G>A
- MANE Select
- NM_001042424
- dbSNP
- rs375995389
- Type
- single nucleotide variant
- Location
- chr4:1918230 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
- Residue 339
- an α-helix
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-glu339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown