Is TEK p.Ile162Phe (c.484A>T) pathogenic?

TEK p.Ile162Phe (c.484A>T) is classified Conflicting classifications of pathogenicity in TEK (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-29). AlphaMissense: likely benign (0.1898); Ultra-rare (popmax 0.033%, mid); Associated with multiple cutaneous and mucosal venous malformations.

What condition is associated with TEK p.Ile162Phe (c.484A>T)?

TEK p.Ile162Phe (c.484A>T) is associated with multiple cutaneous and mucosal venous malformations (ClinVar).

How common is TEK p.Ile162Phe (c.484A>T) in the general population?

TEK p.Ile162Phe (c.484A>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about TEK p.Ile162Phe (c.484A>T)?

AlphaMissense predicts likely benign (score 0.1898) — an in-silico prediction, not a clinical call.

TEK p.Ile162Phe

c.484A>T · rs752000002 · VCV914142

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1898 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple cutaneous and mucosal venous malformations

Computational evidence

Protein change
AlphaMissense	0.1898	likely benign
REVEL	0.239	benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.47	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 0.68, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	24.1	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 0.033% Middle Eastern · 2/6,056 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00285% 46/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,028
South Asian	0.0231%	4,337
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00178%	56,188

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.Ile162Phe
Coding: c.484A>T
MANE Select: NM_000459
dbSNP: rs752000002
Type: single nucleotide variant
Location: chr9:27169485 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 162: 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

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-ile162phe (accessed [today's date]).

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