Is TEK p.Pro304Leu (c.911C>T) pathogenic?

TEK p.Pro304Leu (c.911C>T) is classified Likely benign in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.0955); Ultra-rare (popmax 0.0802%, eas).

How common is TEK p.Pro304Leu (c.911C>T) in the general population?

TEK p.Pro304Leu (c.911C>T) is ultra-rare (popmax 0.0802%, eas) (gnomAD).

What do computational predictors say about TEK p.Pro304Leu (c.911C>T)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

TEK p.Pro304Leu

c.911C>T · rs533028014 · VCV1367960

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.88, phastCons 0.35
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	17.33	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 0.0802% East Asian · 36/44,864 alleles

Filtering AF 0.0595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00254% 41/1,613,778 alleles · ultra-rare exomes 37/1,461,566 · genomes 4/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0802%	1,246
South Asian	0.00549%	18,214

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.Pro304Leu
Coding: c.911C>T
MANE Select: NM_000459
dbSNP: rs533028014
Type: single nucleotide variant
Location: chr9:27180249 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 304: the egf-like 3 domain

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

Similar variants

TEK p.Pro304Ala 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-pro304leu (accessed [today's date]).

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