Is LTBP2 p.Thr802= (c.2406T>C) pathogenic?

LTBP2 p.Thr802= (c.2406T>C) is classified Benign/Likely benign in LTBP2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 50.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Weill-Marchesani syndrome.

What condition is associated with LTBP2 p.Thr802= (c.2406T>C)?

LTBP2 p.Thr802= (c.2406T>C) is associated with Weill-Marchesani syndrome, glaucoma 3, primary congenital, D, Weill-Marchesani syndrome 3 (ClinVar).

LTBP2 p.Thr802=

Q: How common is LTBP2 p.Thr802= (c.2406T>C) in the general population?

LTBP2 p.Thr802= (c.2406T>C) is common (popmax 50.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2406T>C · rs699374 · VCV256097

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 50.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Weill-Marchesani syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -3, phastCons 1
Overall
CADD	5.413	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 50.6% African / African-American · 37,792/74,694 alleles

Filtering AF 50.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 50%

Overall 29.7% 475,162/1,602,476 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	50.6%	2
Admixed American	40.2%	2
East Asian	33.7%	3
Remaining individualsnot grpmax-eligible	30%	3
Middle Eastern	29.9%	3
European (non-Finnish)	28%	4
Finnishnot grpmax-eligible	27.9%	4
South Asian	27%	4
Ashkenazi Jewishnot grpmax-eligible	26.3%	4
Amishnot grpmax-eligible	21.1%	5

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: LTBP2
Protein: p.Thr802=
Coding: c.2406T>C
MANE Select: NM_000428
dbSNP: rs699374
Type: single nucleotide variant
Location: chr14:74526097 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33

Full LTBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Weill-Marchesani syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glaucoma 3, primary congenital, D Weill-Marchesani syndrome 3

Similar variants

LTBP2 c.2389-2A>G Likely pathogenic ★★ same condition
LTBP2 p.Arg299Ter Pathogenic ★★ same condition
LTBP2 p.Cys1438Tyr Likely pathogenic ★★ same condition
LTBP2 c.-55G>A Uncertain significance ★★ same condition
LTBP2 c.-93C>T Uncertain significance ★★ same condition
LTBP2 c.*229C>T Uncertain significance ★★ same condition
LTBP2 p.Ala1359Thr Uncertain significance ★★ same condition
LTBP2 p.Ala733Thr 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/ltbp2-p-thr802 (accessed [today's date]).

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