Is LTBP4 p.Arg484= (c.1452C>G) pathogenic?

LTBP4 p.Arg484= (c.1452C>G) is classified Uncertain significance in LTBP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-02). Ultra-rare (popmax 0.033%, mid); Associated with cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies.

What condition is associated with LTBP4 p.Arg484= (c.1452C>G)?

LTBP4 p.Arg484= (c.1452C>G) is associated with cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies (ClinVar).

How common is LTBP4 p.Arg484= (c.1452C>G) in the general population?

LTBP4 p.Arg484= (c.1452C>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

LTBP4 p.Arg484=

c.1452C>G · rs745624027 · VCV892794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 0.023	GERP 0.61, phastCons 0.8
Overall
CADD	10.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000558% 9/1,613,380 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)	0.000424%	235,960

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: LTBP4
Protein: p.Arg484=
Coding: c.1452C>G
MANE Select: NM_001042545
dbSNP: rs745624027
Type: single nucleotide variant
Location: chr19:40609555 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53
Residue 484: the 'disordered' region

Full LTBP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LTBP4 p.Arg484Cys Uncertain significance ★★ ⚠ same residue
LTBP4 c.1307-2A>G Pathogenic/Likely pathogenic ★★ same condition
LTBP4 p.Arg677Ter Pathogenic/Likely pathogenic ★★ same condition
LTBP4 c.*121C>G Uncertain significance ★★ same condition
LTBP4 p.Ala112Ser Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala124Gly Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala1342Thr Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala207Val 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/ltbp4-p-arg484 (accessed [today's date]).

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