TNFAIP3 p.Pro656=
c.1968G>A · rs146788699 · VCV2168606
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.019 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -5.6 |
| Overall | ||
| CADD | 9.405 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,976 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000991%
16/1,614,056 alleles · very rare
exomes 13/1,461,880 · genomes 3/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,992 |
| East Asian | 0.00223% | 44,882 |
| South Asian | 0.0022% | 45,534 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 0.000763% | 131,112 |
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.Pro656=
- Coding
- c.1968G>A
- MANE Select
- NM_001270508
- dbSNP
- rs146788699
- Type
- single nucleotide variant
- Location
- chr6:137880132 (GRCh38)
- Gene constraint
- LOEUF 0.209 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.86 · 17 PDB
- Residue 656
- the 'interaction with tnip1' region; the 'sufficient for inhibitory activity of tnf-induced nf-kappa-b activity' region
Similar variants
- 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
- TNFAIP3 p.Ala586Val Uncertain significance ★★ ⚠ same type
- TNFAIP3 p.Ala610Thr 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-pro656 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown