Is LTBP2 p.Pro865= (c.2595C>T) pathogenic?

LTBP2 p.Pro865= (c.2595C>T) is classified Likely benign in LTBP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-10). Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with LTBP2 p.Pro865= (c.2595C>T)?

LTBP2 p.Pro865= (c.2595C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP2 p.Pro865= (c.2595C>T) in the general population?

LTBP2 p.Pro865= (c.2595C>T) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

LTBP2 p.Pro865=

c.2595C>T · VCV4049855

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

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 -4.3	GERP -2.1
Overall
CADD	9.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,856 alleles

Filtering AF 0.00545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00143% 23/1,612,722 alleles · ultra-rare exomes 15/1,460,488 · genomes 8/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,551
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,530
Remaining individualsnot grpmax-eligible	0.0032%	31,217
African / African-American	0.00267%	37,456
South Asian	0.0022%	45,400
European (non-Finnish)	0.000763%	131,076

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.Pro865=
Coding: c.2595C>T
MANE Select: NM_000428
Type: single nucleotide variant
Location: chr14:74522854 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33
Residue 865: the egf-like 4 domain

Full LTBP2 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

LTBP2 p.Ala1204Thr Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala1354Val Uncertain significance ★★ same condition
LTBP2 p.Ala1359Val Uncertain significance ★★ same condition
LTBP2 p.Ala141Gly Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala1421Val Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala1734Val Uncertain significance ★★ same condition
LTBP2 p.Ala1767Val Uncertain significance ★★ ⚠ same condition
LTBP2 p.Ala451Asp 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-pro865 (accessed [today's date]).

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