Is TLE6 p.Gly423= (c.1269A>G) pathogenic?

TLE6 p.Gly423= (c.1269A>G) is classified Likely benign in TLE6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-06). Rare (popmax 0.143%, afr); Associated with TLE6-related disorder.

What condition is associated with TLE6 p.Gly423= (c.1269A>G)?

TLE6 p.Gly423= (c.1269A>G) is associated with TLE6-related disorder (ClinVar).

How common is TLE6 p.Gly423= (c.1269A>G) in the general population?

TLE6 p.Gly423= (c.1269A>G) is rare (popmax 0.143%, afr) (gnomAD).

TLE6 p.Gly423=

c.1269A>G · rs147020368 · VCV3046348

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.143%, afr)

Conditions

TLE6-related disorder

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
Overall
CADD	0.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.143% African / African-American · 107/74,890 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.007% 113/1,613,642 alleles · rare exomes 56/1,461,802 · genomes 57/151,840 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.143%	700
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.00334%	29,947

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: TLE6
Protein: p.Gly423=
Coding: c.1269A>G
MANE Select: NM_001143986
dbSNP: rs147020368
Type: single nucleotide variant
Location: chr19:2991867 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.29 · 4 PDB

Full TLE6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TLE6-related disorder

Similar variants

TLE6 c.1387-3T>C Benign same condition
TLE6 c.1615-7C>A Likely benign same condition
TLE6 c.993+8C>T Likely benign same condition
TLE6 p.Ala365= Likely benign same condition
TLE6 p.Asp386= Benign same condition
TLE6 p.Gln487= Likely benign same condition
TLE6 p.Gln6His Benign same condition
TLE6 p.Pro540= Benign 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/tle6-p-gly423 (accessed [today's date]).

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