NSD2 p.Pro777=
c.2331G>A · rs917950554 · VCV1905093
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, 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 -11 | GERP -3.6 |
| Overall | ||
| CADD | 2.154 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,060 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00112%
18/1,608,776 alleles · ultra-rare
exomes 16/1,456,584 · genomes 2/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,020 |
| East Asian | 0.00446% | 22,440 |
| Admixed American | 0.00334% | 29,912 |
| African / African-American | 0.00267% | 37,431 |
| Finnishnot grpmax-eligible | 0.00161% | 62,156 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,354 |
| South Asian | 0.00111% | 90,372 |
| European (non-Finnish) | 0.000509% | 196,347 |
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.Pro777=
- Coding
- c.2331G>A
- MANE Select
- NM_001042424
- dbSNP
- rs917950554
- Type
- single nucleotide variant
- Location
- chr4:1953517 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
- Residue 777
- a UniProt-annotated variant site (in raust)
Similar variants
- NSD2 p.Pro777Leu 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.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
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-pro777 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown