Is LTBP3 p.Cys830Arg (c.2488T>C) pathogenic?

LTBP3 p.Cys830Arg (c.2488T>C) is classified Uncertain significance in LTBP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-21). AlphaMissense: likely pathogenic (0.9968); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Cys830Arg (c.2488T>C)?

LTBP3 p.Cys830Arg (c.2488T>C) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Cys830Arg (c.2488T>C) in the general population?

LTBP3 p.Cys830Arg (c.2488T>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about LTBP3 p.Cys830Arg (c.2488T>C)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

LTBP3 p.Cys830Arg

c.2488T>C · rs1856230265 · VCV1792023

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic · top 7% in LTBP3
REVEL	0.955	strongly pathogenic-leaning
SaProt	LLR -14.26	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 11 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	29.4	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 0.000678% European (non-Finnish) · 8/1,179,980 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,008 alleles · very rare exomes 8/1,461,842 · genomes 0/152,166 · joint denominator

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.Cys830Arg
Coding: c.2488T>C
MANE Select: NM_001130144
dbSNP: rs1856230265
Type: single nucleotide variant
Location: chr11:65543213 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 830: the egf-like 8; 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-cys830arg (accessed [today's date]).

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