Is LTBP3 p.Gln321= (c.963G>A) pathogenic?

LTBP3 p.Gln321= (c.963G>A) is classified Likely benign in LTBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-30). Ultra-rare (popmax 0.0133%, afr); Associated with brachyolmia-amelogenesis imperfecta syndrome.

What condition is associated with LTBP3 p.Gln321= (c.963G>A)?

LTBP3 p.Gln321= (c.963G>A) is associated with brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Gln321= (c.963G>A) in the general population?

LTBP3 p.Gln321= (c.963G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

LTBP3 p.Gln321=

c.963G>A · rs201043285 · VCV1767640

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Conditions

brachyolmia-amelogenesis imperfecta syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.9, phastCons 1
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,968 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000868% 14/1,612,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,497
South Asian	0.0044%	22,752

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.Gln321=
Coding: c.963G>A
MANE Select: NM_001130144
dbSNP: rs201043285
Type: single nucleotide variant
Location: chr11:65553432 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 321: the tb 1 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 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
LTBP3 p.Ala1250Pro Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1289Val 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-gln321 (accessed [today's date]).

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