NSD2 p.Phe87Ile
c.259T>A · VCV4846878
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4123 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Conditions
1
Rauch-Steindl syndrome
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4123 | ambiguous |
|---|---|---|
| REVEL | 0.234 | benign-leaning |
| SaProt | LLR -4.64 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 3,598 bp · p 0.3 · regional, not allelic |
| Overall | ||
| CADD | 23.3 | 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
- NSD2
- Protein
- p.Phe87Ile
- Coding
- c.259T>A
- MANE Select
- NM_001042424
- Type
- single nucleotide variant
- Location
- chr4:1900913 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.22 · 24 PDB
Similar variants
- NSD2 p.Arg450Ter Likely pathogenic ★★ same condition
- NSD2 p.Arg755Ter Pathogenic/Likely pathogenic ★★ same condition
- NSD2 p.Arg935Ter Pathogenic ★★ same condition
- NSD2 p.Glu1363Lys Uncertain significance ★★ ⚠ same condition
- NSD2 p.Phe922Ser Uncertain significance ★★ ⚠ same condition
- NSD2 p.Val435Ala Uncertain significance ★★ ⚠ same condition
- NSD2 p.Pro1341= Benign/Likely benign ★★ same condition
- NSD2 c.2339-1G>A Likely pathogenic ★ same condition
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-phe87ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown