Is LTBP3 p.Pro667= (c.2001C>G) pathogenic?

LTBP3 p.Pro667= (c.2001C>G) is classified Likely benign in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). Very rare (popmax 0.000339%, nfe); Associated with brachyolmia-amelogenesis imperfecta syndrome.

What condition is associated with LTBP3 p.Pro667= (c.2001C>G)?

LTBP3 p.Pro667= (c.2001C>G) is associated with brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Pro667= (c.2001C>G) in the general population?

LTBP3 p.Pro667= (c.2001C>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

LTBP3 p.Pro667=

c.2001C>G · rs2135141886 · VCV3013021

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

brachyolmia-amelogenesis imperfecta syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.419	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.5, phastCons 1
Overall
CADD	3.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,952 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,018 alleles · very rare exomes 4/1,461,756 · genomes 0/152,262 · joint denominator

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.Pro667=
Coding: c.2001C>G
MANE Select: NM_001130144
dbSNP: rs2135141886
Type: single nucleotide variant
Location: chr11:65547545 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 667: the egf-like 5; calcium-binding domain

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.Pro667Ser Uncertain significance ★ ⚠ same residue
LTBP3 p.Pro667Thr 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

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-pro667 (accessed [today's date]).

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