TNFAIP3 p.Pro425=
c.1275G>A · rs373211004 · VCV1934481
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -7.7 | GERP -4.5 |
| Overall | ||
| CADD | 0.114 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,090 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.000991%
16/1,613,972 alleles · very rare
exomes 15/1,461,814 · genomes 1/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,182 |
| European (non-Finnish) | 0.000847% | 118,004 |
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
- TNFAIP3
- Protein
- p.Pro425=
- Coding
- c.1275G>A
- MANE Select
- NM_001270508
- dbSNP
- rs373211004
- Type
- single nucleotide variant
- Location
- chr6:137878720 (GRCh38)
- Gene constraint
- LOEUF 0.209 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.86 · 17 PDB
- Residue 425
- the 'interaction with tnip1' region; the 'interaction with ripk1' region; the 'disordered' region
Similar variants
- TNFAIP3 p.Pro425Leu Uncertain significance ★★ ⚠ same residue
- TNFAIP3 p.Pro425Arg Uncertain significance ★ ⚠ same residue
- TNFAIP3 p.Arg271Ter Pathogenic ★★ same type
- TNFAIP3 p.Arg87Ter Pathogenic ★★ same type
- TNFAIP3 p.Glu366Ter Pathogenic/Likely pathogenic ★★ same type
- TNFAIP3 p.Glu630Ter Pathogenic/Likely pathogenic ★★ same type
- TNFAIP3 p.Trp317Ter Pathogenic/Likely pathogenic ★★ same type
- TNFAIP3 p.Ala327Val 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/tnfaip3-p-pro425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown