Is TEK p.Ser917Ile (c.2750G>T) pathogenic?

TEK p.Ser917Ile (c.2750G>T) is classified Likely pathogenic in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-02). AlphaMissense: likely pathogenic (0.9911); Absent from gnomAD v4.1; Associated with multiple cutaneous and mucosal venous malformations.

What condition is associated with TEK p.Ser917Ile (c.2750G>T)?

TEK p.Ser917Ile (c.2750G>T) is associated with multiple cutaneous and mucosal venous malformations (ClinVar).

How common is TEK p.Ser917Ile (c.2750G>T) in the general population?

TEK p.Ser917Ile (c.2750G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEK p.Ser917Ile (c.2750G>T)?

AlphaMissense predicts likely pathogenic (score 0.9911) — an in-silico prediction, not a clinical call.

TEK p.Ser917Ile

c.2750G>T · rs2488989309 · VCV3238638

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple cutaneous and mucosal venous malformations

Computational evidence

Protein change
AlphaMissense	0.9911	likely pathogenic ✓ concordant with ClinVar · top 9% in TEK
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -14.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 41 bp · p 3.3e-05 · regional, not allelic
Overall
CADD	33.0	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.Ser917Ile
Coding: c.2750G>T
MANE Select: NM_000459
dbSNP: rs2488989309
Type: single nucleotide variant
Location: chr9:27212770 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 917: the protein kinase domain; a UniProt-annotated variant site (found in a patient with solitary sporadic venous malformations; increased ligand-independent autophosphorylation)

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

Disease context

multiple cutaneous and mucosal venous malformations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TEK p.Arg1099Ter Pathogenic ★★ same condition
TEK p.Arg849Trp Pathogenic ★★ ⚠ same condition
TEK p.Arg915Cys Pathogenic/Likely pathogenic ★★ same condition
TEK p.Arg915His Pathogenic/Likely pathogenic ★★ same condition
TEK p.Arg918Cys Pathogenic/Likely pathogenic ★★ same condition
TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same condition
TEK p.Tyr897Asn Pathogenic/Likely pathogenic ★★ ⚠ same condition
TEK p.Tyr897Cys Pathogenic ★★ ⚠ 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-ser917ile (accessed [today's date]).

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