Is TEK p.Ala925Thr (c.2773G>A) pathogenic?

TEK p.Ala925Thr (c.2773G>A) is classified Conflicting classifications of pathogenicity in TEK (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.2906); Ultra-rare (popmax 0.0109%, nfe); Associated with glaucoma 3, primary congenital, E.

What condition is associated with TEK p.Ala925Thr (c.2773G>A)?

TEK p.Ala925Thr (c.2773G>A) is associated with glaucoma 3, primary congenital, E, multiple cutaneous and mucosal venous malformations (ClinVar).

How common is TEK p.Ala925Thr (c.2773G>A) in the general population?

TEK p.Ala925Thr (c.2773G>A) is ultra-rare (popmax 0.0109%, nfe) (gnomAD).

What do computational predictors say about TEK p.Ala925Thr (c.2773G>A)?

AlphaMissense predicts likely benign (score 0.2906) — an in-silico prediction, not a clinical call.

TEK p.Ala925Thr

c.2773G>A · rs138463877 · VCV930496

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2906 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glaucoma 3, primary congenital, E

Computational evidence

Protein change
AlphaMissense	0.2906	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
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 0.62	unconstrained · MANE · 7,337 bp · p 3.9e-07 · regional, not allelic
Overall
CADD	27.0	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

Grpmax group 0.0109% European (non-Finnish) · 129/1,180,022 alleles

Filtering AF 0.00936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0088%

Overall 0.00843% 136/1,613,934 alleles · ultra-rare exomes 118/1,461,850 · genomes 18/152,084 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0109%	9,147
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,012

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.Ala925Thr
Coding: c.2773G>A
MANE Select: NM_000459
dbSNP: rs138463877
Type: single nucleotide variant
Location: chr9:27212793 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 925: the protein kinase domain; an α-helix; a UniProt-annotated variant site (in vmcm; increased ligand-independent autophosphorylation and kinase activation)

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

Also linked: multiple cutaneous and mucosal venous malformations

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-ala925thr (accessed [today's date]).

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