Is LTBP3 p.Arg59= (c.177C>G) pathogenic?

LTBP3 p.Arg59= (c.177C>G) is classified Likely benign in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-05). Very rare (popmax 0.00111%, sas); Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Arg59= (c.177C>G)?

LTBP3 p.Arg59= (c.177C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Arg59= (c.177C>G) in the general population?

LTBP3 p.Arg59= (c.177C>G) is very rare (popmax 0.00111%, sas) (gnomAD).

LTBP3 p.Arg59=

c.177C>G · VCV4049863

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -2.3, phastCons 0.88
Overall
CADD	12.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/89,878 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000189% 3/1,589,612 alleles · very rare exomes 2/1,437,868 · genomes 1/151,744 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	89,878
European (non-Finnish)	0.00017%	587,458

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.Arg59=
Coding: c.177C>G
MANE Select: NM_001130144
Type: single nucleotide variant
Location: chr11:65557783 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21

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.Arg59Gly 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-arg59 (accessed [today's date]).

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