Is TBL3 p.Arg86= (c.258G>A) pathogenic?

TBL3 p.Arg86= (c.258G>A) is classified Benign in TBL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-20). Common (popmax 7.28%, afr) — too common for a highly-penetrant pathogenic allele.

TBL3 p.Arg86=

Q: How common is TBL3 p.Arg86= (c.258G>A) in the general population?

TBL3 p.Arg86= (c.258G>A) is common (popmax 7.28%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.258G>A · rs35189805 · VCV786634

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.28%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP -0.85, phastCons 1
Overall
CADD	7.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.28% African / African-American · 5,463/75,004 alleles

Filtering AF 7.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.06%

Overall 0.376% 6,058/1,609,480 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.28%	14
Remaining individualsnot grpmax-eligible	0.44%	227
Admixed American	0.423%	237
Middle Eastern	0.149%	672
South Asian	0.00771%	12,973
Ashkenazi Jewishnot grpmax-eligible	0.0068%	14,712
European (non-Finnish)	0.00416%	24,023
East Asian	0.00223%	44,766

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: TBL3
Protein: p.Arg86=
Coding: c.258G>A
MANE Select: NM_006453
dbSNP: rs35189805
Type: single nucleotide variant
Location: chr16:1974558 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 3 PDB

Full TBL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TBL3 p.Arg86Gln Uncertain significance ★ ⚠ same residue
TBL3 c.1742+8G>C Benign ★★ same type
NOXO1 c.223+1G>C Uncertain significance ★ ⚠ same type
NOXO1 p.Ala278Val Uncertain significance ★ ⚠ same type
NOXO1 p.Gly312Asp Uncertain significance ★ ⚠ same type
TBL3 p.Ala106Thr Uncertain significance ★ ⚠ same type
TBL3 p.Ala106Val Uncertain significance ★ same type
TBL3 p.Ala158Gly 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/tbl3-p-arg86 (accessed [today's date]).

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