NFIB p.Pro345=
c.1035C>T · VCV4902659
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0318%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 15.35 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0318%
South Asian · 29/91,078 alleles
Filtering AF
0.0228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0196%
Overall
0.00347%
56/1,614,102 alleles · ultra-rare
exomes 48/1,461,824 · genomes 8/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0318% | 3,141 |
| African / African-American | 0.016% | 6,253 |
| East Asian | 0.00223% | 44,868 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.0011% | 90,768 |
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
- NFIB
- Protein
- p.Pro345=
- Coding
- c.1035C>T
- MANE Select
- NM_001190737
- Type
- single nucleotide variant
- Location
- chr9:14125657 (GRCh38)
- Gene constraint
- LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.17 · 2 PDB
- Residue 345
- a UniProt-annotated variant site (in macid); the 'disordered' region
Similar variants
- NFIB p.Pro345Thr Uncertain significance ★ ⚠ same residue
- NFIB p.Arg301Ter Pathogenic/Likely pathogenic ★★ same type
- NFIB p.Arg37Ter Pathogenic ★★ same type
- NFIB p.Arg39Cys Pathogenic/Likely pathogenic ★★ same type
- NFIB p.Arg48Ter Pathogenic/Likely pathogenic ★★ same type
- NFIB p.Arg89Ter Pathogenic/Likely pathogenic ★★ same type
- NFIB p.Gln123Ter Likely pathogenic ★★ same type
- NFIB p.Leu132Pro 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/nfib-p-pro345 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown