Is TEK p.Ser269Ile (c.806G>T) pathogenic?

TEK p.Ser269Ile (c.806G>T) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.1249); Very rare (popmax 0.00666%, amr).

How common is TEK p.Ser269Ile (c.806G>T) in the general population?

TEK p.Ser269Ile (c.806G>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about TEK p.Ser269Ile (c.806G>T)?

AlphaMissense predicts likely benign (score 0.1249) — an in-silico prediction, not a clinical call.

TEK p.Ser269Ile

c.806G>T · rs764047256 · VCV2878534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1249	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -5.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -3.8, phastCons 0.095
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% Admixed American · 4/60,018 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,614,100 alleles · very rare exomes 4/1,461,768 · genomes 0/152,332 · joint denominator

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.Ser269Ile
Coding: c.806G>T
MANE Select: NM_000459
dbSNP: rs764047256
Type: single nucleotide variant
Location: chr9:27173267 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 269: the egf-like 2 domain

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

Similar variants

TEK p.Arg1099Ter Pathogenic ★★ same type
TEK p.Arg849Trp Pathogenic ★★ ⚠ same type
TEK p.Arg915Cys Pathogenic/Likely pathogenic ★★ same type
TEK p.Arg915His Pathogenic/Likely pathogenic ★★ same type
TEK p.Arg918Cys Pathogenic/Likely pathogenic ★★ same type
TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same type
TEK p.Glu1109Ter Pathogenic/Likely pathogenic ★★ same type
TEK p.Tyr897Asn Pathogenic/Likely 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-ser269ile (accessed [today's date]).

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