NFIB p.Ser459Pro
c.1375T>C · VCV3891830
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,513,098)
Conditions
1
macrocephaly, acquired, with impaired intellectual development
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.346 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.6, phastCons 1 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 219 kb · p 0.24 · regional, not allelic |
| Overall | ||
| CADD | 28.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,513,098). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- NFIB
- Protein
- p.Ser459Pro
- Coding
- c.1375T>C
- MANE Select
- NM_001190737
- Type
- single nucleotide variant
- Location
- chr9:14116217 (GRCh38)
- Gene constraint
- LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.17 · 2 PDB
Similar variants
- NFIB p.Arg301Ter Pathogenic/Likely pathogenic ★★ same condition
- NFIB p.Arg37Ter Pathogenic ★★ same condition
- NFIB p.Arg39Cys Pathogenic/Likely pathogenic ★★ same condition
- NFIB p.Arg48Ter Pathogenic/Likely pathogenic ★★ same condition
- NFIB p.Arg89Ter Pathogenic/Likely pathogenic ★★ same condition
- NFIB p.Gln123Ter Likely pathogenic ★★ same condition
- NFIB p.Leu132Pro Pathogenic/Likely pathogenic ★★ same condition
- NFIB p.Lys126Glu Pathogenic/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/nfib-p-ser459pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown