NAF1 p.Pro478=
c.1434T>C · rs763909888 · VCV2961812
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00397%, eas)
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 0.028 | GERP -1.4, phastCons 0.18 |
| Overall | ||
| CADD | 3.981 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00397%
East Asian · 1/25,188 alleles
Overall
0.000269%
2/742,278 alleles · very rare
exomes 1/701,334 · genomes 1/40,944 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00397% | 25,188 |
| European (non-Finnish) | 0.000205% | 488,107 |
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
- NAF1
- Protein
- p.Pro478=
- Coding
- c.1434T>C
- MANE Select
- NM_138386
- dbSNP
- rs763909888
- Type
- single nucleotide variant
- Location
- chr4:163128948 (GRCh38)
- Structure
- AlphaFold pLDDT 72.47 · 8 PDB
- Residue 478
- the 'required for inhibitory activity of tnf-induced nf-kappa-b activation' region; an α-helix; the 'ubiquitin-binding domain (ubd)' region
Similar variants
- TNIP1 p.Ser478Asn Uncertain significance ★ same residue
- NAF1 p.Ala102Ser Uncertain significance ★★ ⚠ same type
- NAF1 p.Ala323Val Uncertain significance ★★ ⚠ same type
- NAF1 p.Ala87Val Uncertain significance ★★ ⚠ same type
- NAF1 p.Arg106Trp Uncertain significance ★★ ⚠ same type
- NAF1 p.Arg437Cys Uncertain significance ★★ ⚠ same type
- NAF1 p.Arg437His Uncertain significance ★★ ⚠ same type
- NAF1 p.Asn17Ser Uncertain significance ★★ ⚠ 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/naf1-p-pro478 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown