Is TLE6 p.Lys269fs (c.805_806del) pathogenic?

TLE6 p.Lys269fs (c.805806del) is classified Likely pathogenic in TLE6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-27). Very rare (popmax 0.0022%, sas); Associated with Preimplantation embryonic lethality 1.

What condition is associated with TLE6 p.Lys269fs (c.805_806del)?

TLE6 p.Lys269fs (c.805_806del) is associated with Preimplantation embryonic lethality 1 (ClinVar).

How common is TLE6 p.Lys269fs (c.805_806del) in the general population?

TLE6 p.Lys269fs (c.805_806del) is very rare (popmax 0.0022%, sas) (gnomAD).

TLE6 p.Lys269fs

c.805_806del · rs752098612 · VCV812696

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Preimplantation embryonic lethality 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.16

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.00031% 5/1,614,124 alleles · very rare exomes 5/1,461,790 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
European (non-Finnish)	0.000254%	393,351

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.Lys269fs
Coding: c.805_806del
MANE Select: NM_001143986
dbSNP: rs752098612
Type: Deletion
Location: chr19:2989124 (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

Preimplantation embryonic lethality 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TLE6 p.Ala378fs Pathogenic/Likely pathogenic ★★ same condition
TLE6 p.Thr126fs Likely pathogenic ★ same condition
TLE6 p.Gln383Ter Likely pathogenic ★ same condition
TLE6 p.Gly352Arg Pathogenic ★ same condition
TLE6 p.Ser510Tyr Likely pathogenic ★ ⚠ same condition
TLE6 p.Glu117Lys Uncertain significance ★ ⚠ same condition
TLE6 c.52-46G>A Likely benign ★ same condition
TLE6 c.1615-5del Likely benign 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/tle6-p-lys269fs (accessed [today's date]).

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