Is TEK p.His234Arg (c.701A>G) pathogenic?

TEK p.His234Arg (c.701A>G) is classified Uncertain significance in TEK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.7045); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with TEK p.His234Arg (c.701A>G)?

TEK p.His234Arg (c.701A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TEK p.His234Arg (c.701A>G) in the general population?

TEK p.His234Arg (c.701A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about TEK p.His234Arg (c.701A>G)?

AlphaMissense predicts likely pathogenic (score 0.7045) — an in-silico prediction, not a clinical call.

TEK p.His234Arg

c.701A>G · VCV4632947

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7045	likely pathogenic
REVEL	0.492	indeterminate
SaProt	LLR -6.64	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	23.7	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 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,613,820 alleles · very rare exomes 18/1,461,498 · genomes 0/152,322 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)	0.00127%	78,649

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.His234Arg
Coding: c.701A>G
MANE Select: NM_000459
Type: single nucleotide variant
Location: chr9:27172688 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 234: the egf-like 1 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.His458Pro Uncertain significance ★★ ⚠ same condition
TEK p.Lys435Gln 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-his234arg (accessed [today's date]).

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