Is LTBP3 p.Ser963= (c.2889C>T) pathogenic?

LTBP3 p.Ser963= (c.2889C>T) is classified Benign/Likely benign in LTBP3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Rare (popmax 0.777%, afr); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Ser963= (c.2889C>T)?

LTBP3 p.Ser963= (c.2889C>T) is associated with Inborn genetic diseases, brachyolmia-amelogenesis imperfecta syndrome (ClinVar).

How common is LTBP3 p.Ser963= (c.2889C>T) in the general population?

LTBP3 p.Ser963= (c.2889C>T) is rare (popmax 0.777%, afr) (gnomAD).

LTBP3 p.Ser963=

c.2889C>T · rs75311576 · VCV464025

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.777%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.247	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -0.75, phastCons 1
Overall
CADD	13.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.777% African / African-American · 583/75,052 alleles

Filtering AF 0.725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.704%

Overall 0.0393% 634/1,612,902 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.777%	129
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0496%	2,015
Admixed American	0.0217%	4,614
South Asian	0.0011%	91,044
European (non-Finnish)	8.48e-05%	1,179,857

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.Ser963=
Coding: c.2889C>T
MANE Select: NM_001130144
dbSNP: rs75311576
Type: single nucleotide variant
Location: chr11:65541130 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 963: the tb 3 domain; a disulfide bond

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 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-ser963 (accessed [today's date]).

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