Is LTBP2 p.Arg324= (c.970A>C) pathogenic?

LTBP2 p.Arg324= (c.970A>C) is classified Conflicting classifications of pathogenicity in LTBP2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-19). Very rare (popmax 0.0011%, nfe); Associated with Weill-Marchesani syndrome.

What condition is associated with LTBP2 p.Arg324= (c.970A>C)?

LTBP2 p.Arg324= (c.970A>C) is associated with Weill-Marchesani syndrome, glaucoma 3, primary congenital, D (ClinVar).

How common is LTBP2 p.Arg324= (c.970A>C) in the general population?

LTBP2 p.Arg324= (c.970A>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

LTBP2 p.Arg324=

c.970A>C · rs372209109 · VCV888132

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

Weill-Marchesani syndrome

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 3.4	GERP 2, phastCons 1
Overall
CADD	13.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,480 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00089% 13/1,460,820 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: LTBP2
Protein: p.Arg324=
Coding: c.970A>C
MANE Select: NM_000428
dbSNP: rs372209109
Type: single nucleotide variant
Location: chr14:74555554 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 324: the 'disordered' region

Full LTBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Weill-Marchesani syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glaucoma 3, primary congenital, D

Similar variants

LTBP2 c.2389-2A>G Likely pathogenic ★★ same condition
LTBP2 p.Arg299Ter Pathogenic ★★ same condition
LTBP2 p.Cys1438Tyr Likely pathogenic ★★ same condition
LTBP2 c.-55G>A Uncertain significance ★★ same condition
LTBP2 c.-93C>T Uncertain significance ★★ same condition
LTBP2 c.*229C>T Uncertain significance ★★ same condition
LTBP2 p.Ala1359Thr Uncertain significance ★★ same condition
LTBP2 p.Ala733Thr 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/ltbp2-p-arg324 (accessed [today's date]).

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