NFIB p.Val220=
c.660A>G · VCV4902676
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.069%, afr)
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 -0.087 | GERP -5.2, phastCons 0.82 |
| Overall | ||
| CADD | 2.812 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.069%
African / African-American · 51/73,890 alleles
Filtering AF
0.0539%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0485%
Overall
0.00705%
112/1,587,654 alleles · ultra-rare
exomes 76/1,435,348 · genomes 36/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.069% | 1,449 |
| Middle Eastern | 0.05% | 2,000 |
| Admixed American | 0.0197% | 5,073 |
| Remaining individualsnot grpmax-eligible | 0.00975% | 10,258 |
| European (non-Finnish) | 0.00352% | 28,437 |
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.Val220=
- Coding
- c.660A>G
- MANE Select
- NM_001190737
- Type
- single nucleotide variant
- Location
- chr9:14155850 (GRCh38)
- Gene constraint
- LOEUF 0.3 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.17 · 2 PDB
- Residue 220
- a UniProt-annotated variant site (in macid)
Similar variants
- 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
- NFIB p.Lys126Glu 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-val220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown