Is TEK p.Met952Val (c.2854A>G) pathogenic?

TEK p.Met952Val (c.2854A>G) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-28). AlphaMissense: likely pathogenic (0.9492); Very rare (popmax 8.47e-05%, nfe); Associated with glaucoma 3, primary congenital, E.

What condition is associated with TEK p.Met952Val (c.2854A>G)?

TEK p.Met952Val (c.2854A>G) is associated with glaucoma 3, primary congenital, E (ClinVar).

How common is TEK p.Met952Val (c.2854A>G) in the general population?

TEK p.Met952Val (c.2854A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about TEK p.Met952Val (c.2854A>G)?

AlphaMissense predicts likely pathogenic (score 0.9492) — an in-silico prediction, not a clinical call.

TEK p.Met952Val

c.2854A>G · VCV4293288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glaucoma 3, primary congenital, E

Computational evidence

Protein change
AlphaMissense	0.9492	likely pathogenic
REVEL	0.75	pathogenic-leaning
SaProt	LLR -12.12	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,337 bp · p 3.9e-07 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.2e-05% 1/1,613,984 alleles · very rare exomes 1/1,461,688 · genomes 0/152,296 · 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.Met952Val
Coding: c.2854A>G
MANE Select: NM_000459
Type: single nucleotide variant
Location: chr9:27212874 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 952: the protein kinase domain; an α-helix

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

Disease context

glaucoma 3, primary congenital, E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same condition
TEK p.Arg1076Trp Uncertain significance ★★ ⚠ same condition
TEK c.2209+17A>G Benign ★★ same condition
TEK c.3063-49C>T Benign ★★ same condition
TEK c.761-40C>T Benign ★★ same condition
TEK p.Gln346Pro Benign ★★ same condition
TEK p.Ser654= Benign ★★ same condition
TEK c.1490-1G>A Likely 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-met952val (accessed [today's date]).

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