Is LTBP3 p.Pro549= (c.1647G>A) pathogenic?

LTBP3 p.Pro549= (c.1647G>A) is classified Likely benign in LTBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-15). Very rare (popmax 0.00391%, amr); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Pro549= (c.1647G>A)?

LTBP3 p.Pro549= (c.1647G>A) is associated with Inborn genetic diseases, brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Pro549= (c.1647G>A) in the general population?

LTBP3 p.Pro549= (c.1647G>A) is very rare (popmax 0.00391%, amr) (gnomAD).

LTBP3 p.Pro549=

c.1647G>A · rs778135144 · VCV2880247

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00391%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.009	GERP -3.2, phastCons 0.33
Overall
CADD	13.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00391% Admixed American · 2/51,158 alleles

Filtering AF 0.000648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000452% 7/1,549,860 alleles · very rare exomes 7/1,397,638 · genomes 0/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00391%	25,579
Remaining individualsnot grpmax-eligible	0.00166%	60,162
European (non-Finnish)	0.000349%	286,943

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.Pro549=
Coding: c.1647G>A
MANE Select: NM_001130144
dbSNP: rs778135144
Type: single nucleotide variant
Location: chr11:65551199 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 549: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: brachyolmia-amelogenesis imperfecta syndrome

Similar variants

LTBP3 p.Pro549Ala Uncertain significance ★★ ⚠ same residue
LTBP3 p.Pro549Leu Uncertain significance ★ ⚠ same residue
LTBP3 p.Pro549fs Pathogenic ★ 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

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-pro549 (accessed [today's date]).

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