Is TLE6 p.Gly352Arg (c.1054G>C) pathogenic?

TLE6 p.Gly352Arg (c.1054G>C) is classified Pathogenic in TLE6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-02). AlphaMissense: likely pathogenic (0.9257); Absent from gnomAD v4.1; Associated with Preimplantation embryonic lethality 1.

What condition is associated with TLE6 p.Gly352Arg (c.1054G>C)?

TLE6 p.Gly352Arg (c.1054G>C) is associated with Preimplantation embryonic lethality 1 (ClinVar).

How common is TLE6 p.Gly352Arg (c.1054G>C) in the general population?

TLE6 p.Gly352Arg (c.1054G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TLE6 p.Gly352Arg (c.1054G>C)?

AlphaMissense predicts likely pathogenic (score 0.9257) — an in-silico prediction, not a clinical call.

TLE6 p.Gly352Arg

c.1054G>C · rs1376982287 · VCV1691503

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9257 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Preimplantation embryonic lethality 1

Computational evidence

Protein change
AlphaMissense	0.9257	likely pathogenic ✓ concordant with ClinVar · top 2% in TLE6
REVEL	0.434	indeterminate
SaProt	LLR -14.46	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 17 kb · p 0.00048 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TLE6
Protein: p.Gly352Arg
Coding: c.1054G>C
MANE Select: NM_001143986
dbSNP: rs1376982287
Type: single nucleotide variant
Location: chr19:2989595 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.29 · 4 PDB
Residue 352: 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

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

Similar variants

TLE6 p.Gln383Ter Likely 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-gly352arg (accessed [today's date]).

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