Is LTBP4 p.Pro1157Ser (c.3469C>T) pathogenic?

LTBP4 p.Pro1157Ser (c.3469C>T) is classified Uncertain significance in LTBP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely pathogenic (0.9011); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LTBP4 p.Pro1157Ser (c.3469C>T)?

LTBP4 p.Pro1157Ser (c.3469C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP4 p.Pro1157Ser (c.3469C>T) in the general population?

LTBP4 p.Pro1157Ser (c.3469C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LTBP4 p.Pro1157Ser (c.3469C>T)?

AlphaMissense predicts likely pathogenic (score 0.9011) — an in-silico prediction, not a clinical call.

LTBP4 p.Pro1157Ser

c.3469C>T · VCV3292260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9011 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9011	likely pathogenic
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -10.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 6,878 bp · p 8.7e-07 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1224S vs ClinVar P1157S) — verify the residue.

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: LTBP4
Protein: p.Pro1157Ser
Coding: c.3469C>T
MANE Select: NM_001042545
Type: single nucleotide variant
Location: chr19:40622652 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53
Residue 1224 UniProt numbering: the tb 3 domain

Full LTBP4 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

LTBP4 p.Pro1157Leu Uncertain significance ★★ ⚠ same residue
LTBP4 p.Pro1157= Likely benign ★★ same residue
LTBP4 p.Ala182Thr Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala207Val Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala23Val Uncertain significance ★★ same condition
LTBP4 p.Ala775Val Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala796Gly Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala967Pro 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-pro1157ser (accessed [today's date]).

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