Is TEK p.Gln346Pro (c.1037A>C) pathogenic?

TEK p.Gln346Pro (c.1037A>C) is classified Benign in TEK (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0515); Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with multiple cutaneous and mucosal venous malformations.

What do computational predictors say about TEK p.Gln346Pro (c.1037A>C)?

AlphaMissense predicts likely benign (score 0.0515) — an in-silico prediction, not a clinical call.

TEK p.Gln346Pro

Q: What condition is associated with TEK p.Gln346Pro (c.1037A>C)?

TEK p.Gln346Pro (c.1037A>C) is associated with multiple cutaneous and mucosal venous malformations, glaucoma 3, primary congenital, E (ClinVar).

Q: How common is TEK p.Gln346Pro (c.1037A>C) in the general population?

TEK p.Gln346Pro (c.1037A>C) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1037A>C · rs682632 · VCV1284626

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0515 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple cutaneous and mucosal venous malformations

Computational evidence

Protein change
AlphaMissense	0.0515	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -5.36	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 3.3	GERP -1.4, phastCons 0.98
Regional constraint	o/e 0.81	unconstrained · MANE · 76 kb · p 8.9e-06 · regional, not allelic
Overall
CADD	17.35	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 100% East Asian · 44,871/44,874 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 96.7% 1,559,828/1,613,674 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
African / African-American	99.4%	1
Admixed American	98.7%	1
Middle Eastern	98.4%	1
Ashkenazi Jewishnot grpmax-eligible	98.3%	1
South Asian	98.3%	1
Finnishnot grpmax-eligible	97.1%	1
Remaining individualsnot grpmax-eligible	97%	1
European (non-Finnish)	96%	1
Amishnot grpmax-eligible	94.6%	1

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.Gln346Pro
Coding: c.1037A>C
MANE Select: NM_000459
dbSNP: rs682632
Type: single nucleotide variant
Location: chr9:27183465 (GRCh38)
Gene constraint: LOEUF 0.368 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 17 PDB
Residue 346: a UniProt-annotated variant site (in)

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

Disease context

multiple cutaneous and mucosal venous malformations — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glaucoma 3, primary congenital, E

Similar variants

TEK p.Gln346Ser Uncertain significance ★ same residue
TEK p.Arg1099Ter Pathogenic ★★ same condition
TEK p.Arg849Trp Pathogenic ★★ ⚠ same condition
TEK p.Arg915Cys Pathogenic/Likely pathogenic ★★ same condition
TEK p.Arg915His Pathogenic/Likely pathogenic ★★ same condition
TEK p.Arg918Cys Pathogenic/Likely pathogenic ★★ same condition
TEK p.Gln518Ter Pathogenic/Likely pathogenic ★★ same condition
TEK p.Tyr897Asn Pathogenic/Likely pathogenic ★★ ⚠ 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-gln346pro (accessed [today's date]).

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