Is TEK p.Ser1033Arg (c.3099C>G) pathogenic?

TEK p.Ser1033Arg (c.3099C>G) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-15). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1.

How common is TEK p.Ser1033Arg (c.3099C>G) in the general population?

TEK p.Ser1033Arg (c.3099C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEK p.Ser1033Arg (c.3099C>G)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

TEK p.Ser1033Arg

c.3099C>G · VCV4902825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 2% in TEK
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -12.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.32	donor loss · deltas
Pangolin	Δ0.30	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 7,337 bp · p 3.9e-07 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TEK
Protein: p.Ser1033Arg
Coding: c.3099C>G
MANE Select: NM_000459
Type: single nucleotide variant
Location: chr9:27218813 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 1033: the protein kinase domain

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

Similar variants

TEK p.Ser1033= Uncertain significance ★ same residue
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

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-ser1033arg (accessed [today's date]).

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