Is TEK p.Met322Val (c.964A>G) pathogenic?

TEK p.Met322Val (c.964A>G) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with TEK p.Met322Val (c.964A>G)?

TEK p.Met322Val (c.964A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TEK p.Met322Val (c.964A>G) in the general population?

TEK p.Met322Val (c.964A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about TEK p.Met322Val (c.964A>G)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

TEK p.Met322Val

c.964A>G · rs749678742 · VCV2404588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -4.64	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	GERP -3.5, phastCons 0.045
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	1.397	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00134% African / African-American · 1/74,804 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,590 alleles · very rare exomes 8/1,461,672 · genomes 1/151,918 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,804
European (non-Finnish)	0.000678%	147,484

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.Met322Val
Coding: c.964A>G
MANE Select: NM_000459
dbSNP: rs749678742
Type: single nucleotide variant
Location: chr9:27180302 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 322: a β-strand; the egf-like 3 domain

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-met322val (accessed [today's date]).

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