NSD2 p.Pro895=
c.2685G>A · rs771145606 · VCV1926145
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.075 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -0.25, phastCons 1 |
| Overall | ||
| CADD | 12.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,994 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000991%
16/1,613,932 alleles · ultra-rare
exomes 13/1,461,756 · genomes 3/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.01% | 9,999 |
| East Asian | 0.00668% | 14,969 |
| South Asian | 0.00329% | 30,359 |
| African / African-American | 0.00267% | 37,449 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 8.47e-05% | 1,180,048 |
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.Pro895=
- Coding
- c.2685G>A
- MANE Select
- NM_001042424
- dbSNP
- rs771145606
- Type
- single nucleotide variant
- Location
- chr4:1955992 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
- Residue 895
- the pwwp 2 domain; a UniProt-annotated variant site (in raust); a UniProt-annotated variant site (in raust; decreased histone methyltransferase activity h3-k36 specific)
Similar variants
- NSD2 p.Pro895Leu Pathogenic ★★ same residue
- NSD2 p.Pro895Ser Uncertain significance ★ ⚠ 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.Ala320Thr Uncertain significance ★★ ⚠ same type
- NSD2 p.Ala383Gly Uncertain significance ★★ ⚠ same type
- NSD2 p.Ala693Asp 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-pro895 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown