Is LTBP3 p.Asp596Ala (c.1787A>C) pathogenic?

LTBP3 p.Asp596Ala (c.1787A>C) is classified Uncertain significance in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely benign (0.1264); Very rare (popmax 0.000847%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Asp596Ala (c.1787A>C)?

LTBP3 p.Asp596Ala (c.1787A>C) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Asp596Ala (c.1787A>C) in the general population?

LTBP3 p.Asp596Ala (c.1787A>C) is very rare (popmax 0.000847%, nfe) (gnomAD).

What do computational predictors say about LTBP3 p.Asp596Ala (c.1787A>C)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

LTBP3 p.Asp596Ala

c.1787A>C · rs746874069 · VCV2488638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -1, phastCons 1
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000847% European (non-Finnish) · 10/1,179,962 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,613,572 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.Asp596Ala
Coding: c.1787A>C
MANE Select: NM_001130144
dbSNP: rs746874069
Type: single nucleotide variant
Location: chr11:65547979 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 596: a disulfide bond; the egf-like 3 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.Asp596Glu Uncertain significance ★ ⚠ same residue
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

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-asp596ala (accessed [today's date]).

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