Is LTBP4 p.Arg901= (c.2701C>A) pathogenic?

LTBP4 p.Arg901= (c.2701C>A) is classified Likely benign in LTBP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-09). Very rare (popmax 0.00223%, eas); Associated with LTBP4-related disorder.

What condition is associated with LTBP4 p.Arg901= (c.2701C>A)?

LTBP4 p.Arg901= (c.2701C>A) is associated with LTBP4-related disorder (ClinVar).

How common is LTBP4 p.Arg901= (c.2701C>A) in the general population?

LTBP4 p.Arg901= (c.2701C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

LTBP4 p.Arg901=

c.2701C>A · rs2515368558 · VCV3051980

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

LTBP4-related disorder

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 0.64	GERP -0.26, phastCons 1
Overall
CADD	9.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,842 alleles

Overall 6.25e-05% 1/1,599,656 alleles · very rare exomes 1/1,447,454 · genomes 0/152,202 · joint denominator

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: LTBP4
Protein: p.Arg901=
Coding: c.2701C>A
MANE Select: NM_001042545
dbSNP: rs2515368558
Type: single nucleotide variant
Location: chr19:40614335 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53
Residue 901: the egf-like 10; calcium-binding domain

Full LTBP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

LTBP4-related disorder

Similar variants

LTBP4 p.Arg901Pro Uncertain significance ★★ same residue
LTBP4 p.Glu1460Ala Uncertain significance ★★ ⚠ same condition
LTBP4 p.Thr1306Ala Uncertain significance ★★ ⚠ same condition
LTBP4 p.Val1109= Benign ★★ same condition
LTBP4 p.Cys589Ter Likely pathogenic ★ same condition
LTBP4 p.Glu1044Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
LTBP4 p.Ser772Arg Uncertain significance ★ ⚠ same condition
LTBP4 p.Trp1285Cys 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/ltbp4-p-arg901 (accessed [today's date]).

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