Is LTBP2 p.Arg905= (c.2715C>T) pathogenic?

LTBP2 p.Arg905= (c.2715C>T) is classified Benign/Likely benign in LTBP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.73%, nfe); Associated with Weill-Marchesani syndrome.

What condition is associated with LTBP2 p.Arg905= (c.2715C>T)?

LTBP2 p.Arg905= (c.2715C>T) is associated with Weill-Marchesani syndrome, glaucoma 3, primary congenital, D (ClinVar).

How common is LTBP2 p.Arg905= (c.2715C>T) in the general population?

LTBP2 p.Arg905= (c.2715C>T) is low-frequency (popmax 3.73%, nfe) (gnomAD).

LTBP2 p.Arg905=

c.2715C>T · rs7145480 · VCV884794

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.73%, 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 -4.2	GERP -2.7
Overall
CADD	2.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.73% European (non-Finnish) · 43,993/1,179,936 alleles

Filtering AF 3.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.69%

Overall 3.15% 50,899/1,614,088 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.73%	27
Admixed American	3.38%	30
Remaining individualsnot grpmax-eligible	2.99%	33
Middle Eastern	2.71%	37
Finnishnot grpmax-eligible	1.9%	53
Ashkenazi Jewishnot grpmax-eligible	1.48%	67
African / African-American	0.752%	133
South Asian	0.683%	146
East Asian	0.00668%	14,960

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.Arg905=
Coding: c.2715C>T
MANE Select: NM_000428
dbSNP: rs7145480
Type: single nucleotide variant
Location: chr14:74521984 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 905: a disulfide bond; the egf-like 5; calcium-binding domain

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 p.Arg905His Uncertain significance ★★ ⚠ same residue
LTBP2 p.Arg905Cys Uncertain significance ★ ⚠ same residue
LTBP3 p.His905Gln 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

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-arg905 (accessed [today's date]).

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