Is LTBP3 p.Pro45fs (c.132del) pathogenic?

LTBP3 p.Pro45fs (c.132del) is classified Pathogenic in LTBP3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2022-01-03). Very rare (popmax 0.00292%, afr); Associated with brachyolmia-amelogenesis imperfecta syndrome.

What condition is associated with LTBP3 p.Pro45fs (c.132del)?

LTBP3 p.Pro45fs (c.132del) is associated with brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Pro45fs (c.132del) in the general population?

LTBP3 p.Pro45fs (c.132del) is very rare (popmax 0.00292%, afr) (gnomAD).

LTBP3 p.Pro45fs

c.132del · rs1286042594 · VCV523637

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00292%, afr)

Conditions

brachyolmia-amelogenesis imperfecta syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 0.92, phastCons 1
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(CGCCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00292% African / African-American · 2/68,580 alleles

Filtering AF 0.000484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000181%

Overall 0.000547% 8/1,462,020 alleles · very rare exomes 6/1,311,052 · genomes 2/150,968 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00461%	21,691
African / African-Americangrpmax	0.00292%	34,290
South Asian	0.00267%	37,495
European (non-Finnish)	0.00018%	554,053

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro45fs
Coding: c.132del
MANE Select: NM_001130144
dbSNP: rs1286042594
Type: Deletion
Location: chr11:65557828 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21

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 c.1187-25_1187del Likely pathogenic ★ same condition
LTBP3 c.1531+2del Likely pathogenic ★ same condition
LTBP3 c.646_661+26del Likely pathogenic ★ same condition
LTBP3 p.Ala163fs Pathogenic ★ same condition
LTBP3 p.Ala777fs Pathogenic ★ same condition
LTBP3 p.Arg5fs Pathogenic ★ same condition
LTBP3 p.Asn746fs Likely pathogenic ★ same condition
LTBP3 p.Cys1223_Val1224insTer 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/ltbp3-p-pro45fs (accessed [today's date]).

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