Is TNFAIP3 p.Pro765= (c.2295C>T) pathogenic?

TNFAIP3 p.Pro765= (c.2295C>T) is classified Benign/Likely benign in TNFAIP3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Common (popmax 8.93%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autoinflammatory syndrome, familial, Behcet-like 1.

What condition is associated with TNFAIP3 p.Pro765= (c.2295C>T)?

TNFAIP3 p.Pro765= (c.2295C>T) is associated with autoinflammatory syndrome, familial, Behcet-like 1 (ClinVar).

TNFAIP3 p.Pro765=

Q: How common is TNFAIP3 p.Pro765= (c.2295C>T) in the general population?

TNFAIP3 p.Pro765= (c.2295C>T) is common (popmax 8.93%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2295C>T · rs5029956 · VCV776164

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 8.93%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

autoinflammatory syndrome, familial, Behcet-like 1

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 -20	GERP -5
Overall
CADD	0.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.93% African / African-American · 6,638/74,320 alleles

Filtering AF 8.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.68%

Overall 0.482% 7,712/1,601,274 alleles · common exomes 3,640/1,449,242 · genomes 4,072/152,032 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.93%	11
Admixed American	0.79%	127
Remaining individualsnot grpmax-eligible	0.653%	153
Middle Eastern	0.266%	375
South Asian	0.0178%	5,632
European (non-Finnish)	0.0158%	6,312
East Asian	0.00224%	44,570

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.Pro765=
Coding: c.2295C>T
MANE Select: NM_001270508
dbSNP: rs5029956
Type: single nucleotide variant
Location: chr6:137881241 (GRCh38)
Gene constraint: LOEUF 0.209 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.86 · 17 PDB
Residue 765: the 'interaction with tnip1' region; the 'sufficient for inhibitory activity of tnf-induced nf-kappa-b activity' region; the 'required for lysosomal localization and for traf2 lysosomal degradation' region

Full TNFAIP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoinflammatory syndrome, familial, Behcet-like 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TNFAIP3 p.Arg271Ter Pathogenic ★★ same condition
TNFAIP3 p.Arg87Ter Pathogenic ★★ same condition
TNFAIP3 p.Glu366Ter Pathogenic/Likely pathogenic ★★ same condition
TNFAIP3 p.Ala717Thr Uncertain significance ★★ ⚠ same condition
TNFAIP3 p.Arg439Gln Uncertain significance ★★ ⚠ same condition
TNFAIP3 p.Arg569Gln Uncertain significance ★★ ⚠ same condition
TNFAIP3 p.Arg61Trp Uncertain significance ★★ same condition
TNFAIP3 p.Arg660Lys Uncertain significance ★★ ⚠ 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/tnfaip3-p-pro765 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown