Is TEK p.Lys89Asn (c.267G>T) pathogenic?

TEK p.Lys89Asn (c.267G>T) is classified Conflicting classifications of pathogenicity in TEK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-21). AlphaMissense: ambiguous (0.4121); Very rare (popmax 0.00492%, nfe); Associated with multiple cutaneous and mucosal venous malformations.

What condition is associated with TEK p.Lys89Asn (c.267G>T)?

TEK p.Lys89Asn (c.267G>T) is associated with multiple cutaneous and mucosal venous malformations (ClinVar).

How common is TEK p.Lys89Asn (c.267G>T) in the general population?

TEK p.Lys89Asn (c.267G>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about TEK p.Lys89Asn (c.267G>T)?

AlphaMissense predicts ambiguous (score 0.4121) — an in-silico prediction, not a clinical call.

TEK p.Lys89Asn

c.267G>T · rs764880845 · VCV913743

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4121 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Conditions

multiple cutaneous and mucosal venous malformations

Computational evidence

Protein change
AlphaMissense	0.4121	ambiguous
REVEL	0.326	indeterminate
SaProt	LLR -7.10	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 0.98, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.00492% European (non-Finnish) · 58/1,180,024 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00366% 59/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,345
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Lys89Asn
Coding: c.267G>T
MANE Select: NM_000459
dbSNP: rs764880845
Type: single nucleotide variant
Location: chr9:27158045 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 89: a disulfide bond; a UniProt-annotated variant site (in glc3e; formation of protein aggregates); the ig-like c2-type 1 domain

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-lys89asn (accessed [today's date]).

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