NFIX p.Ala246=
c.738G>A · rs780269313 · VCV1314797
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00246%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.032 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -3.7 | GERP -3.4 |
| Overall | ||
| CADD | 8.071 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00246%
European (non-Finnish) · 29/1,179,862 alleles
Filtering AF
0.00172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.00211%
34/1,613,918 alleles · very rare
exomes 34/1,461,686 · genomes 0/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00246% | 40,685 |
| East Asian | 0.00223% | 44,880 |
| South Asian | 0.0022% | 45,541 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
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.Ala246=
- Coding
- c.738G>A
- MANE Select
- NM_001365902
- dbSNP
- rs780269313
- Type
- single nucleotide variant
- Location
- chr19:13073946 (GRCh38)
- Gene constraint
- LOEUF 0.092 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 62.94 · 3 PDB
Similar variants
- NFIX p.Ala246Val Uncertain significance ★ ⚠ same residue
- NFIX c.559+1G>A Pathogenic ★★ same type
- NFIX c.697+1G>A Pathogenic/Likely pathogenic ★★ same type
- NFIX c.818+1G>A Likely pathogenic ★★ same type
- NFIX c.955+1G>A Pathogenic ★★ same type
- NFIX c.955+1G>T Pathogenic ★★ same type
- NFIX p.Arg115Gln Pathogenic/Likely pathogenic ★★ same type
- NFIX p.Arg116Gln 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/nfix-p-ala246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown