Is TEK p.Pro243Leu (c.728C>T) pathogenic?

TEK p.Pro243Leu (c.728C>T) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-01). AlphaMissense: likely pathogenic (0.6678); Absent from gnomAD v4.1.

How common is TEK p.Pro243Leu (c.728C>T) in the general population?

TEK p.Pro243Leu (c.728C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TEK p.Pro243Leu (c.728C>T)?

AlphaMissense predicts likely pathogenic (score 0.6678) — an in-silico prediction, not a clinical call.

TEK p.Pro243Leu

c.728C>T · rs1824004002 · VCV932603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6678 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6678	likely pathogenic
REVEL	0.443	indeterminate
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	27.2	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

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.Pro243Leu
Coding: c.728C>T
MANE Select: NM_000459
dbSNP: rs1824004002
Type: single nucleotide variant
Location: chr9:27172715 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 243: the egf-like 1 domain

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

Similar variants

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
TEK p.Tyr897Asn 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-pro243leu (accessed [today's date]).

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