Is TEK p.Phe1085Val (c.3253T>G) pathogenic?

TEK p.Phe1085Val (c.3253T>G) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-21). AlphaMissense: likely pathogenic (0.9739); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TEK p.Phe1085Val (c.3253T>G)?

TEK p.Phe1085Val (c.3253T>G) is associated with Inborn genetic diseases (ClinVar).

How common is TEK p.Phe1085Val (c.3253T>G) in the general population?

TEK p.Phe1085Val (c.3253T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEK p.Phe1085Val (c.3253T>G)?

AlphaMissense predicts likely pathogenic (score 0.9739) — an in-silico prediction, not a clinical call.

TEK p.Phe1085Val

c.3253T>G · rs1483739145 · VCV2256306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9739 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9739	likely pathogenic
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -14.52	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 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,108 bp · p 0.68 · regional, not allelic
Overall
CADD	29.8	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.Phe1085Val
Coding: c.3253T>G
MANE Select: NM_000459
dbSNP: rs1483739145
Type: single nucleotide variant
Location: chr9:27228258 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 1085: the protein kinase domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TEK p.Ala621Ser Uncertain significance ★★ ⚠ same condition
TEK p.Ala945Thr Uncertain significance ★★ ⚠ same condition
TEK p.Arg119His Uncertain significance ★★ ⚠ same condition
TEK p.Arg673His Uncertain significance ★★ ⚠ same condition
TEK p.Asn299Asp Uncertain significance ★★ ⚠ same condition
TEK p.Gly743Arg Uncertain significance ★★ ⚠ same condition
TEK p.His234Arg Uncertain significance ★★ ⚠ same condition
TEK p.His458Pro Uncertain significance ★★ ⚠ 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-phe1085val (accessed [today's date]).

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