Is LTBP3 p.Pro418= (c.1254A>C) pathogenic?

LTBP3 p.Pro418= (c.1254A>C) is classified Likely benign in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Pro418= (c.1254A>C)?

LTBP3 p.Pro418= (c.1254A>C) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Pro418= (c.1254A>C) in the general population?

LTBP3 p.Pro418= (c.1254A>C) is absent from gnomAD v4.1 (gnomAD).

LTBP3 p.Pro418=

c.1254A>C · VCV3541092

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.049	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -3.9
Overall
CADD	2.838	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LTBP3
Protein: p.Pro418=
Coding: c.1254A>C
MANE Select: NM_001130144
Type: single nucleotide variant
Location: chr11:65552339 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 418: a disulfide bond; the tb 2 domain

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

Similar variants

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
LTBP3 p.Ala144Ser Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala144Thr Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala147Val 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-pro418 (accessed [today's date]).

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