Is TEK p.Tyr897Phe (c.2690A>T) pathogenic?

TEK p.Tyr897Phe (c.2690A>T) is classified Pathogenic in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-13). AlphaMissense: likely benign (0.3331); Absent from gnomAD v4.1; Associated with Venous malformation.

What condition is associated with TEK p.Tyr897Phe (c.2690A>T)?

TEK p.Tyr897Phe (c.2690A>T) is associated with Venous malformation (ClinVar).

How common is TEK p.Tyr897Phe (c.2690A>T) in the general population?

TEK p.Tyr897Phe (c.2690A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEK p.Tyr897Phe (c.2690A>T)?

AlphaMissense predicts likely benign (score 0.3331) — an in-silico prediction, not a clinical call.

TEK p.Tyr897Phe

c.2690A>T · VCV4279984

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3331 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Venous malformation

Computational evidence

Protein change
AlphaMissense	0.3331	likely benign ⚠ discordant with ClinVar
REVEL	0.658	pathogenic-leaning
SaProt	LLR -5.54	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 6,039 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	24.6	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: TEK
Protein: p.Tyr897Phe
Coding: c.2690A>T
MANE Select: NM_000459
Type: single nucleotide variant
Location: chr9:27212710 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 897: the protein kinase domain; a β-strand; a UniProt-annotated variant site (in vmcm; increased ligand-independent autophosphorylation and kinase activation); a UniProt-annotated variant site (found in a patient with multiple sporadic venous malformations; increased ligand-independent autophosphorylation); a UniProt-annotated variant site (found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation); a UniProt-annotated variant site (in vmcm; also found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation and kinase activation)

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

Disease context

Venous malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TEK p.Tyr897Asn Pathogenic/Likely pathogenic ★★ ⚠ same residue
TEK p.Tyr897Cys Pathogenic ★★ ⚠ same residue
TEK p.Tyr897His Pathogenic ★★ ⚠ same residue
TEK p.Tyr897Ser Pathogenic/Likely pathogenic ★★ ⚠ same residue
TEK p.Lys1110fs Likely pathogenic ★ same condition
TEK p.Thr1105fs Likely pathogenic ★ same condition
TEK p.Arg1099Ter Pathogenic ★★ same type
TEK p.Arg849Trp Pathogenic ★★ ⚠ 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/tek-p-tyr897phe (accessed [today's date]).

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