Is TEK p.Arg673Cys (c.2017C>T) pathogenic?

TEK p.Arg673Cys (c.2017C>T) is classified Uncertain significance in TEK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.1676); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with TEK p.Arg673Cys (c.2017C>T)?

TEK p.Arg673Cys (c.2017C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TEK p.Arg673Cys (c.2017C>T) in the general population?

TEK p.Arg673Cys (c.2017C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about TEK p.Arg673Cys (c.2017C>T)?

AlphaMissense predicts likely benign (score 0.1676) — an in-silico prediction, not a clinical call.

TEK p.Arg673Cys

c.2017C>T · rs749958421 · VCV2382943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1676 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1676	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 21 kb · p 0.78 · regional, not allelic
Overall
CADD	29.6	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 0.00534% African / African-American · 4/74,882 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,613,902 alleles · very rare exomes 22/1,461,818 · genomes 3/152,084 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,720
South Asian	0.00439%	22,768
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asian	0.00223%	44,876
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.0011%	90,770

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.Arg673Cys
Coding: c.2017C>T
MANE Select: NM_000459
dbSNP: rs749958421
Type: single nucleotide variant
Location: chr9:27202927 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 673: the fibronectin type-iii 3 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.Arg673His Uncertain significance ★★ ⚠ same residue
TEK p.Ala621Ser Uncertain significance ★★ ⚠ same condition
TEK p.Ala945Thr Uncertain significance ★★ ⚠ same condition
TEK p.Arg119His 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-arg673cys (accessed [today's date]).

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