NFIX p.Leu19=
c.55C>T · rs1253804251 · VCV2953979
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
2
Marshall-Smith syndrome
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 4.9 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 15.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,080 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000669%
Overall
0.000248%
4/1,612,854 alleles · ultra-rare
exomes 3/1,460,620 · genomes 1/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,080 |
| Admixed American | 0.00501% | 19,945 |
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
- NFIX
- Protein
- p.Leu19=
- Coding
- c.55C>T
- MANE Select
- NM_001365902
- dbSNP
- rs1253804251
- Type
- single nucleotide variant
- Location
- chr19:13025048 (GRCh38)
- Gene constraint
- LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.94 · 3 PDB
- Residue 19
- a DNA-binding region; an α-helix
Similar variants
- NFIX c.697+1G>A Pathogenic/Likely pathogenic ★★ same condition
- NFIX c.818+1G>A Likely pathogenic ★★ same condition
- NFIX c.955+1G>A Pathogenic ★★ same condition
- NFIX c.955+1G>T Pathogenic ★★ same condition
- NFIX p.Arg116Gln Pathogenic/Likely pathogenic ★★ same condition
- NFIX p.Arg116Trp Pathogenic ★★ same condition
- NFIX p.Arg128Gln Likely pathogenic ★★ same condition
- NFIX p.Arg128Trp 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/nfix-p-leu19 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown