Is LTBP3 p.Pro399= (c.1197G>A) pathogenic?

LTBP3 p.Pro399= (c.1197G>A) is classified Likely benign in LTBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-11). Ultra-rare (popmax 0.024%, afr); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Pro399= (c.1197G>A)?

LTBP3 p.Pro399= (c.1197G>A) is associated with Inborn genetic diseases, brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Pro399= (c.1197G>A) in the general population?

LTBP3 p.Pro399= (c.1197G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

LTBP3 p.Pro399=

c.1197G>A · rs371960878 · VCV1548877

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.208	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.6
Overall
CADD	3.273	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/74,912 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00267% 43/1,613,366 alleles · ultra-rare exomes 35/1,461,204 · genomes 8/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,162
Middle Eastern	0.0165%	6,072
East Asian	0.00668%	14,961
European (non-Finnish)	0.00169%	58,999
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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.Pro399=
Coding: c.1197G>A
MANE Select: NM_001130144
dbSNP: rs371960878
Type: single nucleotide variant
Location: chr11:65552396 (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

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

Also linked: brachyolmia-amelogenesis imperfecta syndrome

Similar variants

LTBP3 p.Pro399Gln Uncertain significance ★★ ⚠ same residue
LTBP3 p.Pro399Leu 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-pro399 (accessed [today's date]).

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