Is TBX2 p.Val263= (c.789C>T) pathogenic?

TBX2 p.Val263= (c.789C>T) is classified Benign/Likely benign in TBX2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-01). Rare (popmax 0.577%, mid).

How common is TBX2 p.Val263= (c.789C>T) in the general population?

TBX2 p.Val263= (c.789C>T) is rare (popmax 0.577%, mid) (gnomAD).

TBX2 p.Val263=

c.789C>T · rs140013823 · VCV734746

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.577%, mid)

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 1.7	GERP -1.5, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.577% Middle Eastern · 35/6,062 alleles

Filtering AF 0.427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.375%

Overall 0.113% 1,825/1,613,416 alleles · rare exomes 1,657/1,461,024 · genomes 168/152,392 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.737%	136
Middle Easterngrpmax	0.577%	173
Remaining individualsnot grpmax-eligible	0.182%	548
Admixed American	0.147%	682
European (non-Finnish)	0.111%	904
Finnishnot grpmax-eligible	0.0348%	2,875
African / African-American	0.032%	3,128
South Asian	0.0209%	4,794

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TBX2
Protein: p.Val263=
Coding: c.789C>T
MANE Select: NM_005994
dbSNP: rs140013823
Type: single nucleotide variant
Location: chr17:61403186 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.13
Residue 263: a DNA-binding region

Full TBX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TBX2 p.Arg20Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
TBX2 p.Ala374Thr Uncertain significance ★★ ⚠ same type
TBX2 p.Arg185His Uncertain significance ★★ ⚠ same type
TBX2 p.Arg616Trp Uncertain significance ★★ ⚠ same type
TBX2 p.Gly536Arg Uncertain significance ★★ same type
TBX2 p.Leu304Val Uncertain significance ★★ ⚠ same type
TBX2 p.Lys148Gln Uncertain significance ★★ ⚠ same type
TBX2 p.Pro39Gln 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/tbx2-p-val263 (accessed [today's date]).

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