Is LTBP2 p.Pro269= (c.807C>T) pathogenic?

LTBP2 p.Pro269= (c.807C>T) is classified Conflicting classifications of pathogenicity in LTBP2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-01). Rare (popmax 0.468%, nfe); Associated with glaucoma 3, primary congenital, D.

What condition is associated with LTBP2 p.Pro269= (c.807C>T)?

LTBP2 p.Pro269= (c.807C>T) is associated with glaucoma 3, primary congenital, D, Weill-Marchesani syndrome (ClinVar).

How common is LTBP2 p.Pro269= (c.807C>T) in the general population?

LTBP2 p.Pro269= (c.807C>T) is rare (popmax 0.468%, nfe) (gnomAD).

LTBP2 p.Pro269=

c.807C>T · rs61738024 · VCV715782

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.468%, nfe)

Conditions

glaucoma 3, primary congenital, D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP -1.5
Overall
CADD	6.161	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.468% European (non-Finnish) · 5,523/1,179,282 alleles

Filtering AF 0.458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.454%

Overall 0.374% 6,039/1,613,314 alleles · rare exomes 5,716/1,461,080 · genomes 323/152,234 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.468%	214
Remaining individualsnot grpmax-eligible	0.373%	268
South Asian	0.149%	670
Admixed American	0.123%	811
Middle Eastern	0.0661%	1,513
African / African-American	0.0626%	1,596
Finnishnot grpmax-eligible	0.0281%	3,557
East Asian	0.00668%	14,961
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592

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.Pro269=
Coding: c.807C>T
MANE Select: NM_000428
dbSNP: rs61738024
Type: single nucleotide variant
Location: chr14:74585877 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 269: the 'disordered' region

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

Disease context

glaucoma 3, primary congenital, D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Weill-Marchesani syndrome

Similar variants

LTBP3 p.Arg269Gly Uncertain significance ★★ ⚠ same residue
LTBP3 p.Arg269Gln Uncertain significance ★ ⚠ same residue
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

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-pro269 (accessed [today's date]).

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