Is TBL2 p.Val269= (c.807G>T) pathogenic?

TBL2 p.Val269= (c.807G>T) is classified Likely benign in TBL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-02-07). Very rare (popmax 0.0011%, sas).

How common is TBL2 p.Val269= (c.807G>T) in the general population?

TBL2 p.Val269= (c.807G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

TBL2 p.Val269=

c.807G>T · rs1584024119 · VCV724587

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, 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 -3.8	GERP -3.7
Overall
CADD	0.459	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,090 alleles

Overall 6.19e-05% 1/1,614,232 alleles · very rare exomes 1/1,461,886 · genomes 0/152,346 · joint denominator

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: TBL2
Protein: p.Val269=
Coding: c.807G>T
MANE Select: NM_012453
dbSNP: rs1584024119
Type: single nucleotide variant
Location: chr7:73571260 (GRCh38)
Gene constraint: LOEUF 1.054 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.11

Full TBL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TBL2 p.Ala189= Benign/Likely benign ★★ same type
TBL2 p.Ala332= Benign/Likely benign ★★ same type
TBL2 p.Gln229= Benign ★★ same type
TBL2 p.Glu135= Benign ★★ same type
TBL2 p.Glu257Ala Benign ★★ same type
TBL2 c.599-7C>A Uncertain significance ★ same type
TBL2 p.Ala139Thr Uncertain significance ★ ⚠ same type
TBL2 p.Ala139Val 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/tbl2-p-val269 (accessed [today's date]).

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