Is LTBP3 p.Pro288= (c.864G>T) pathogenic?

LTBP3 p.Pro288= (c.864G>T) is classified Conflicting classifications of pathogenicity in LTBP3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-23). Ultra-rare (popmax 0.082%, afr); Associated with brachyolmia-amelogenesis imperfecta syndrome.

What condition is associated with LTBP3 p.Pro288= (c.864G>T)?

LTBP3 p.Pro288= (c.864G>T) is associated with brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Pro288= (c.864G>T) in the general population?

LTBP3 p.Pro288= (c.864G>T) is ultra-rare (popmax 0.082%, afr) (gnomAD).

LTBP3 p.Pro288=

c.864G>T · rs201987018 · VCV1483733

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.082%, afr)

Conditions

brachyolmia-amelogenesis imperfecta 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 -7.9	GERP -3.8
Overall
CADD	0.628	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.082% African / African-American · 61/74,364 alleles

Filtering AF 0.0655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.00445% 70/1,574,738 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.082%	1,219
Remaining individualsnot grpmax-eligible	0.00651%	15,354
Admixed American	0.00533%	18,773
South Asian	0.00114%	87,562
European (non-Finnish)	8.56e-05%	1,168,084

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: LTBP3
Protein: p.Pro288=
Coding: c.864G>T
MANE Select: NM_001130144
dbSNP: rs201987018
Type: single nucleotide variant
Location: chr11:65553701 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 288: the tb 1 domain; a disulfide bond

Full LTBP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

brachyolmia-amelogenesis imperfecta syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LTBP3 p.Pro288Arg Uncertain significance ⚠ same residue
LTBP3 c.1063+1G>T Likely pathogenic ★★ same condition
LTBP3 c.3629-3C>T Uncertain significance ★★ same condition
LTBP3 c.3761-2A>G Uncertain significance ★★ same condition
LTBP3 p.Ala1149Thr Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1153Val Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1182Val Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1250Pro 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/ltbp3-p-pro288 (accessed [today's date]).

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