Is TLE6 p.Gln383Ter (c.1147C>T) pathogenic?

TLE6 p.Gln383Ter (c.1147C>T) is classified Likely pathogenic in TLE6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). Ultra-rare (popmax 0.0165%, mid); Associated with Preimplantation embryonic lethality 1.

What condition is associated with TLE6 p.Gln383Ter (c.1147C>T)?

TLE6 p.Gln383Ter (c.1147C>T) is associated with Preimplantation embryonic lethality 1 (ClinVar).

How common is TLE6 p.Gln383Ter (c.1147C>T) in the general population?

TLE6 p.Gln383Ter (c.1147C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

TLE6 p.Gln383Ter

c.1147C>T · VCV4849455

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Preimplantation embryonic lethality 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.62	phastCons 0.96
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Overall 6.2e-05% 1/1,614,206 alleles · ultra-rare exomes 1/1,461,860 · 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: TLE6
Protein: p.Gln383Ter
Coding: c.1147C>T
MANE Select: NM_001143986
Type: single nucleotide variant
Location: chr19:2989688 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.29 · 4 PDB
Residue 383: a β-strand

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.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 p.Ala378fs Pathogenic/Likely pathogenic ★★ same condition
TLE6 p.Thr126fs Likely pathogenic ★ same condition
TLE6 p.Lys269fs Likely pathogenic same condition
TLE6 p.Ala207Thr 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/tle6-p-gln383ter (accessed [today's date]).

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