NSD1 p.Pro2574=
c.7722G>A · rs183751052 · VCV2053629
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
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 -1.3 | GERP -4 |
| Overall | ||
| CADD | 0.254 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,832 alleles
Filtering AF
0.00178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000892%
Overall
0.00105%
17/1,611,532 alleles · very rare
exomes 13/1,459,274 · genomes 4/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00669% | 14,944 |
| Admixed American | 0.00502% | 19,925 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0034% | 29,416 |
| African / African-American | 0.00134% | 74,878 |
| European (non-Finnish) | 0.000764% | 130,936 |
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
- NSD1
- Protein
- p.Pro2574=
- Coding
- c.7722G>A
- MANE Select
- NM_022455
- dbSNP
- rs183751052
- Type
- single nucleotide variant
- Location
- chr5:177295090 (GRCh38)
- Gene constraint
- LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 45.26 · 4 PDB
- Residue 2574
- the 'disordered' region
Similar variants
- NSD1 p.Pro2574Ala Uncertain significance ★ ⚠ same residue
- NSD1 p.Pro2574Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- NSD1 c.1064-2A>G Pathogenic/Likely pathogenic ★★ same type
- NSD1 c.3921+1G>A Likely pathogenic ★★ same type
- NSD1 c.4192+2T>G Pathogenic ★★ same type
- NSD1 c.4303-1G>C Likely pathogenic ★★ same type
- NSD1 c.4378+1G>A Pathogenic/Likely pathogenic ★★ same type
- NSD1 c.4766-2A>G Pathogenic/Likely 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/nsd1-p-pro2574 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown