Is LTBP4 p.Arg91= (c.273G>C) pathogenic?

LTBP4 p.Arg91= (c.273G>C) is classified Conflicting classifications of pathogenicity in LTBP4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-28). Absent from gnomAD v4.1; Associated with cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies.

What condition is associated with LTBP4 p.Arg91= (c.273G>C)?

LTBP4 p.Arg91= (c.273G>C) is associated with cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies (ClinVar).

How common is LTBP4 p.Arg91= (c.273G>C) in the general population?

LTBP4 p.Arg91= (c.273G>C) is absent from gnomAD v4.1 (gnomAD).

LTBP4 p.Arg91=

c.273G>C · rs2081413206 · VCV893560

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,259,050)

Conditions

cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies

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 -1.3	GERP -2.7
Overall
CADD	1.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,259,050). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LTBP4
Protein: p.Arg91=
Coding: c.273G>C
MANE Select: NM_001042545 · reported on NM_003573
dbSNP: rs2081413206
Type: single nucleotide variant
Location: chr19:40600110 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53

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.Arg91Gln Uncertain significance ★ ⚠ same residue
LTBP4 p.Arg91Trp 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

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-arg91 (accessed [today's date]).

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