Is LTBP3 p.Ala438= (c.1314G>A) pathogenic?

LTBP3 p.Ala438= (c.1314G>A) is classified Likely benign in LTBP3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-01). Rare (popmax 0.167%, nfe); Associated with brachyolmia-amelogenesis imperfecta syndrome.

What condition is associated with LTBP3 p.Ala438= (c.1314G>A)?

LTBP3 p.Ala438= (c.1314G>A) is associated with brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Ala438= (c.1314G>A) in the general population?

LTBP3 p.Ala438= (c.1314G>A) is rare (popmax 0.167%, nfe) (gnomAD).

LTBP3 p.Ala438=

c.1314G>A · rs140740739 · VCV707462

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.167%, nfe)

Conditions

brachyolmia-amelogenesis imperfecta syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.213	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -3.9
Overall
CADD	0.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% European (non-Finnish) · 1,973/1,180,002 alleles

Filtering AF 0.161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.136% 2,193/1,614,112 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.167%	598
Remaining individualsnot grpmax-eligible	0.136%	735
South Asian	0.114%	876
African / African-American	0.0267%	3,752
Middle Eastern	0.0165%	6,062
Admixed American	0.0117%	8,575
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
East Asian	0.00223%	44,878
Finnishnot grpmax-eligible	0.00156%	63,992

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.Ala438=
Coding: c.1314G>A
MANE Select: NM_001130144
dbSNP: rs140740739
Type: single nucleotide variant
Location: chr11:65552279 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 438: a disulfide bond; the tb 2 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.Ala438Thr Uncertain significance ★★ ⚠ same residue
LTBP3 p.Ala438Val Benign ★★ same residue
LTBP3 p.Ala438Met 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

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-ala438 (accessed [today's date]).

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