NSD1 p.Pro2136=
c.6408A>G · rs771993179 · VCV1212039
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, 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 -0.67 | GERP -4.5 |
| Overall | ||
| CADD | 1.618 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,080 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.00254%
41/1,614,062 alleles · ultra-rare
exomes 39/1,461,876 · genomes 2/152,186 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,040 |
| European (non-Finnish) | 0.0033% | 30,257 |
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.Pro2136=
- Coding
- c.6408A>G
- MANE Select
- NM_022455
- dbSNP
- rs771993179
- Type
- single nucleotide variant
- Location
- chr5:177292103 (GRCh38)
- Gene constraint
- LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 45.26 · 4 PDB
Similar variants
- NSD1 p.Pro2136Ser Uncertain significance ★ same residue
- NSD1 p.Pro2136fs Pathogenic ★ 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-pro2136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown