NSD2 p.Ile192=
c.576C>T · rs138137147 · VCV348427
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0849%, mid)
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 0.49 | GERP 1.4, phastCons 0.001 |
| Overall | ||
| CADD | 8.469 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0849%
Middle Eastern · 5/5,888 alleles
Filtering AF
0.0334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0216%
Overall
0.00664%
105/1,580,196 alleles · ultra-rare
exomes 89/1,427,974 · genomes 16/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0849% | 1,178 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0297% | 3,372 |
| Remaining individualsnot grpmax-eligible | 0.0131% | 7,615 |
| European (non-Finnish) | 0.00668% | 14,966 |
| South Asian | 0.00472% | 21,166 |
| Admixed American | 0.00189% | 52,982 |
| African / African-American | 0.00137% | 73,230 |
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.Ile192=
- Coding
- c.576C>T
- MANE Select
- NM_001042424
- dbSNP
- rs138137147
- Type
- single nucleotide variant
- Location
- chr4:1901230 (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-ile192 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown