Is LTBP2 p.Gln83= (c.249G>A) pathogenic?

LTBP2 p.Gln83= (c.249G>A) is classified Conflicting classifications of pathogenicity in LTBP2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-12). Very rare (popmax 0.00338%, sas); Associated with Weill-Marchesani syndrome.

What condition is associated with LTBP2 p.Gln83= (c.249G>A)?

LTBP2 p.Gln83= (c.249G>A) is associated with Weill-Marchesani syndrome, glaucoma 3, primary congenital, D (ClinVar).

How common is LTBP2 p.Gln83= (c.249G>A) in the general population?

LTBP2 p.Gln83= (c.249G>A) is very rare (popmax 0.00338%, sas) (gnomAD).

LTBP2 p.Gln83=

c.249G>A · rs779279335 · VCV314318

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 0.00338%, sas)

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 0.22	GERP 1.1, phastCons 0.01
Overall
CADD	6.679	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00338% South Asian · 3/88,760 alleles

Filtering AF 0.000898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000449%

Overall 0.000252% 4/1,584,170 alleles · very rare exomes 4/1,431,870 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00338%	29,587
European (non-Finnish)	8.54e-05%	1,171,490

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.Gln83=
Coding: c.249G>A
MANE Select: NM_000428
dbSNP: rs779279335
Type: single nucleotide variant
Location: chr14:74611696 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 83: 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

LTBP3 p.Ser83Gly Uncertain significance ★ ⚠ same residue
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

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-gln83 (accessed [today's date]).

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