Is TEK p.Lys145fs (c.434del) pathogenic?

TEK p.Lys145fs (c.434del) is classified Likely pathogenic in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 0.00017%, nfe); Associated with glaucoma 3, primary congenital, E.

What condition is associated with TEK p.Lys145fs (c.434del)?

TEK p.Lys145fs (c.434del) is associated with glaucoma 3, primary congenital, E (ClinVar).

How common is TEK p.Lys145fs (c.434del) in the general population?

TEK p.Lys145fs (c.434del) is very rare (popmax 0.00017%, nfe) (gnomAD).

TEK p.Lys145fs

c.434del · rs2490101786 · VCV2582395

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

glaucoma 3, primary congenital, E

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,836 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,566 alleles · very rare

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: TEK
Protein: p.Lys145fs
Coding: c.434del
MANE Select: NM_000459
dbSNP: rs2490101786
Type: Deletion
Location: chr9:27168560 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 145: a UniProt-annotated variant site (in glc3e; formation of protein aggregates); a β-strand

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

Disease context

glaucoma 3, primary congenital, E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TEK p.Tyr193fs Likely pathogenic ★ same condition
TEK p.Val429fs Likely pathogenic ★ same condition
TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same condition
TEK p.Leu444fs Likely pathogenic ★★ same condition
TEK p.Arg1076Trp Uncertain significance ★★ ⚠ same condition
TEK c.2209+17A>G Benign ★★ same condition
TEK c.3063-49C>T Benign ★★ same condition
TEK c.761-40C>T 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/tek-p-lys145fs (accessed [today's date]).

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