NSD1 p.Phe153Ser
c.458T>C · VCV4748562
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2599 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2599 | likely benign |
|---|---|---|
| REVEL | 0.672 | pathogenic-leaning |
| SaProt | LLR -4.08 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 2.6, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 57 kb · p 0.65 · regional, not allelic |
| Overall | ||
| CADD | 24.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- NSD1
- Protein
- p.Phe153Ser
- Coding
- c.458T>C
- MANE Select
- NM_022455
- Type
- single nucleotide variant
- Location
- chr5:177135561 (GRCh38)
- Gene constraint
- LOEUF 0.144 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 45.26 · 4 PDB
Similar variants
- 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
- NSD1 c.4966+1G>A Pathogenic ★★ same type
- NSD1 c.4966+1G>C 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-phe153ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown