Is TLE6 p.Gln487= (c.1461A>G) pathogenic?

TLE6 p.Gln487= (c.1461A>G) is classified Likely benign in TLE6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Rare (popmax 0.143%, eas); Associated with TLE6-related disorder.

What condition is associated with TLE6 p.Gln487= (c.1461A>G)?

TLE6 p.Gln487= (c.1461A>G) is associated with TLE6-related disorder (ClinVar).

How common is TLE6 p.Gln487= (c.1461A>G) in the general population?

TLE6 p.Gln487= (c.1461A>G) is rare (popmax 0.143%, eas) (gnomAD).

TLE6 p.Gln487=

c.1461A>G · rs374858414 · VCV3040040

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.143%, eas)

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 0.014
Overall
CADD	0.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.143% East Asian · 63/44,040 alleles

Filtering AF 0.115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.00758% 121/1,597,238 alleles · rare exomes 103/1,445,016 · genomes 18/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.143%	699
Remaining individualsnot grpmax-eligible	0.0845%	1,184
Admixed American	0.00507%	19,729
South Asian	0.0011%	90,508
European (non-Finnish)	0.000171%	583,669

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.Gln487=
Coding: c.1461A>G
MANE Select: NM_001143986
dbSNP: rs374858414
Type: single nucleotide variant
Location: chr19:2993506 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.29 · 4 PDB
Residue 487: a UniProt-annotated variant site (in ozema15; uncertain significance); a β-strand

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.Gln6His Benign same condition
TLE6 p.Gly423= Likely 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-gln487 (accessed [today's date]).

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