Is LTBP3 p.Ser218Pro (c.652T>C) pathogenic?

LTBP3 p.Ser218Pro (c.652T>C) is classified Uncertain significance in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-26). AlphaMissense: likely benign (0.2724); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Ser218Pro (c.652T>C)?

LTBP3 p.Ser218Pro (c.652T>C) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Ser218Pro (c.652T>C) in the general population?

LTBP3 p.Ser218Pro (c.652T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LTBP3 p.Ser218Pro (c.652T>C)?

AlphaMissense predicts likely benign (score 0.2724) — an in-silico prediction, not a clinical call.

LTBP3 p.Ser218Pro

c.652T>C · rs2496177364 · VCV1754076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2724	likely benign
REVEL	0.557	indeterminate
SaProt	LLR -5.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.27, phastCons 1
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: LTBP3
Protein: p.Ser218Pro
Coding: c.652T>C
MANE Select: NM_001130144
dbSNP: rs2496177364
Type: single nucleotide variant
Location: chr11:65554060 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21

Full LTBP3 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

LTBP3 p.Ala1149Thr Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1153Val Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1182Val Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1250Pro Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala1289Val Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala144Ser Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala144Thr Uncertain significance ★★ ⚠ same condition
LTBP3 p.Ala147Val 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/ltbp3-p-ser218pro (accessed [today's date]).

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