NFIX p.Pro14=
c.42G>A · rs966713031 · VCV1980223
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Conditions
2
Malan overgrowth 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 3.9 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 14.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,742 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000249%
4/1,608,060 alleles · very rare
exomes 2/1,455,998 · genomes 2/152,062 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,742 |
| European (non-Finnish) | 0.000255% | 392,469 |
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.Pro14=
- Coding
- c.42G>A
- MANE Select
- NM_001365902
- dbSNP
- rs966713031
- Type
- single nucleotide variant
- Location
- chr19:13025035 (GRCh38)
- Gene constraint
- LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.94 · 3 PDB
- Residue 14
- a DNA-binding region; an α-helix
Similar variants
- NFIX p.Pro14Arg Uncertain significance ★ ⚠ same residue
- 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
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-pro14 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown