Is TNF p.Arg29= (c.87G>T) pathogenic?

TNF p.Arg29= (c.87G>T) is classified Benign in TNF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-18). Common (popmax 5.29%, afr) — too common for a highly-penetrant pathogenic allele.

TNF p.Arg29=

Q: How common is TNF p.Arg29= (c.87G>T) in the general population?

TNF p.Arg29= (c.87G>T) is common (popmax 5.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.87G>T · rs2228088 · VCV784495

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.29%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.5	GERP -3.4, phastCons 0.001
Overall
CADD	1.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.29% African / African-American · 3,959/74,908 alleles

Filtering AF 5.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.09%

Overall 0.287% 4,631/1,612,698 alleles · common exomes 2,333/1,460,418 · genomes 2,298/152,280 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.29%	19
Middle Eastern	0.479%	209
Remaining individualsnot grpmax-eligible	0.445%	225
Admixed American	0.404%	247
South Asian	0.0616%	1,624
European (non-Finnish)	0.00568%	17,603

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: TNF
Protein: p.Arg29=
Coding: c.87G>T
MANE Select: NM_000594
dbSNP: rs2228088
Type: single nucleotide variant
Location: chr6:31575828 (GRCh38)
Gene constraint: LOEUF 0.592 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 84.72 · 52 PDB

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

Similar variants

TNF p.Pro84Leu Benign/Likely benign ★★ same type
TNF p.Arg107Leu Uncertain significance ★ ⚠ same type
TNF p.Asp66Asn Uncertain significance ★ ⚠ same type
TNF p.Gly184Arg Uncertain significance ★ ⚠ same type
TNF p.Gly54Glu Uncertain significance ★ ⚠ same type
TNF p.Gly57Ser Uncertain significance ★ ⚠ same type
TNF p.Met6Lys Uncertain significance ★ ⚠ same type
TNF p.Thr83Asn 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/tnf-p-arg29 (accessed [today's date]).

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