Is LTBP2 p.Pro537= (c.1611T>G) pathogenic?

LTBP2 p.Pro537= (c.1611T>G) is classified Likely benign in LTBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-10). Absent from gnomAD v4.1.

How common is LTBP2 p.Pro537= (c.1611T>G) in the general population?

LTBP2 p.Pro537= (c.1611T>G) is absent from gnomAD v4.1 (gnomAD).

LTBP2 p.Pro537=

c.1611T>G · VCV3645322

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.31	GERP -3.1, phastCons 0.001
Overall
CADD	4.925	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LTBP2
Protein: p.Pro537=
Coding: c.1611T>G
MANE Select: NM_000428
Type: single nucleotide variant
Location: chr14:74551139 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 537: the 'disordered' region

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

Similar variants

LTBP2 p.Pro537Ala Uncertain significance ★★ ⚠ same residue
LTBP2 p.Pro537Thr Uncertain significance ★ ⚠ same residue
LTBP3 p.Arg537Gln Uncertain significance ★ ⚠ same residue
LTBP3 p.Arg537Trp Uncertain significance ★ ⚠ same residue
LTBP2 c.2389-2A>G Likely pathogenic ★★ same type
LTBP2 c.2659+2T>C Likely pathogenic ★★ same type
LTBP2 c.2789-1G>A Likely pathogenic ★★ same type
LTBP2 c.2789-2A>T Likely pathogenic ★★ same type

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-pro537 (accessed [today's date]).

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