Is TEK p.Val106Ile (c.316G>A) pathogenic?

TEK p.Val106Ile (c.316G>A) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.0841); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with TEK p.Val106Ile (c.316G>A)?

TEK p.Val106Ile (c.316G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TEK p.Val106Ile (c.316G>A) in the general population?

TEK p.Val106Ile (c.316G>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about TEK p.Val106Ile (c.316G>A)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

TEK p.Val106Ile

c.316G>A · rs760650172 · VCV2269775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -3.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	20.2	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 0.0156% East Asian · 7/44,900 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00118% 19/1,614,036 alleles · ultra-rare exomes 17/1,461,868 · genomes 2/152,168 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,414
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00134%	74,906
European (non-Finnish)	0.000847%	118,001

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.Val106Ile
Coding: c.316G>A
MANE Select: NM_000459
dbSNP: rs760650172
Type: single nucleotide variant
Location: chr9:27158094 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 106: a UniProt-annotated variant site (in glc3e; formation of protein aggregates); the ig-like c2-type 1 domain; a β-strand

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-val106ile (accessed [today's date]).

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