Is TEK p.Glu103Asp (c.309A>C) pathogenic?

TEK p.Glu103Asp (c.309A>C) is classified Conflicting classifications of pathogenicity in TEK (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2022-07-20). AlphaMissense: ambiguous (0.4734); Rare (popmax 0.704%, sas); Associated with glaucoma 3, primary infantile, B.

What condition is associated with TEK p.Glu103Asp (c.309A>C)?

TEK p.Glu103Asp (c.309A>C) is associated with glaucoma 3, primary infantile, B, multiple cutaneous and mucosal venous malformations, glaucoma 3, primary congenital, E (ClinVar).

How common is TEK p.Glu103Asp (c.309A>C) in the general population?

TEK p.Glu103Asp (c.309A>C) is rare (popmax 0.704%, sas) (gnomAD).

What do computational predictors say about TEK p.Glu103Asp (c.309A>C)?

AlphaMissense predicts ambiguous (score 0.4734) — an in-silico prediction, not a clinical call.

TEK p.Glu103Asp

c.309A>C · rs572527340 · VCV366393

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.4734 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.704%, sas)

Conditions

glaucoma 3, primary infantile, B

Computational evidence

Protein change
AlphaMissense	0.4734	ambiguous
REVEL	0.418	indeterminate
SaProt	LLR -10.58	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.74, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	21.3	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 0.704% South Asian · 641/91,078 alleles

Filtering AF 0.659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.641%

Overall 0.0436% 703/1,614,190 alleles · rare exomes 670/1,461,874 · genomes 33/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.704%	142
Remaining individualsnot grpmax-eligible	0.0464%	2,156
Middle Eastern	0.033%	3,031
Admixed American	0.00333%	30,016
African / African-American	0.00267%	37,520
European (non-Finnish)	0.00229%	43,704

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.Glu103Asp
Coding: c.309A>C
MANE Select: NM_000459
dbSNP: rs572527340
Type: single nucleotide variant
Location: chr9:27158087 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 103: a UniProt-annotated variant site (in glc3e; formation of protein aggregates); the ig-like c2-type 1 domain; a β-strand

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

Disease context

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

Also linked: multiple cutaneous and mucosal venous malformations glaucoma 3, primary congenital, E

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-glu103asp (accessed [today's date]).

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