Is LTBP3 p.Ser403Arg (c.1209C>A) pathogenic?

LTBP3 p.Ser403Arg (c.1209C>A) is classified Uncertain significance in LTBP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-22). AlphaMissense: likely pathogenic (0.8945); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LTBP3 p.Ser403Arg (c.1209C>A)?

LTBP3 p.Ser403Arg (c.1209C>A) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP3 p.Ser403Arg (c.1209C>A) in the general population?

LTBP3 p.Ser403Arg (c.1209C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LTBP3 p.Ser403Arg (c.1209C>A)?

AlphaMissense predicts likely pathogenic (score 0.8945) — an in-silico prediction, not a clinical call.

LTBP3 p.Ser403Arg

c.1209C>A · VCV4825733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8945 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8945	likely pathogenic
REVEL	0.476	indeterminate
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP -2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 1,631 bp · p 1.2e-10 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

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.Ser403Arg
Coding: c.1209C>A
MANE Select: NM_001130144
Type: single nucleotide variant
Location: chr11:65552384 (GRCh38)
Gene constraint: LOEUF 0.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.21
Residue 403: the tb 2 domain

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.Ser403= Likely benign ★ same residue
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

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-ser403arg (accessed [today's date]).

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