Is LTBP3 p.Cys809Phe (c.2426G>T) pathogenic?

LTBP3 p.Cys809Phe (c.2426G>T) is classified Uncertain significance in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-21). AlphaMissense: likely pathogenic (0.9939); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Cys809Phe (c.2426G>T)?

LTBP3 p.Cys809Phe (c.2426G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Cys809Phe (c.2426G>T) in the general population?

LTBP3 p.Cys809Phe (c.2426G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about LTBP3 p.Cys809Phe (c.2426G>T)?

AlphaMissense predicts likely pathogenic (score 0.9939) — an in-silico prediction, not a clinical call.

LTBP3 p.Cys809Phe

c.2426G>T · VCV4844130

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9939	likely pathogenic · top 10% in LTBP3
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -15.60	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Overall
CADD	28.4	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,990 alleles

Overall 6.84e-05% 1/1,461,864 alleles · very rare

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.Cys809Phe
Coding: c.2426G>T
MANE Select: NM_001130144
Type: single nucleotide variant
Location: chr11:65543477 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 809: the egf-like 7; calcium-binding 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

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-cys809phe (accessed [today's date]).

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