Is LTBP4 p.Pro823Ser (c.2467C>T) pathogenic?

LTBP4 p.Pro823Ser (c.2467C>T) is classified Uncertain significance in LTBP4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.7972); Ultra-rare (popmax 0.0493%, mid); Associated with Inborn genetic diseases.

What condition is associated with LTBP4 p.Pro823Ser (c.2467C>T)?

LTBP4 p.Pro823Ser (c.2467C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP4 p.Pro823Ser (c.2467C>T) in the general population?

LTBP4 p.Pro823Ser (c.2467C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about LTBP4 p.Pro823Ser (c.2467C>T)?

AlphaMissense predicts likely pathogenic (score 0.7972) — an in-silico prediction, not a clinical call.

LTBP4 p.Pro823Ser

c.2467C>T · rs780942572 · VCV451639

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7972 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7972	likely pathogenic
REVEL	0.442	indeterminate
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 9,612 bp · p 0.91 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P890S vs ClinVar P823S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,080 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.02%

Overall 0.00274% 44/1,604,770 alleles · ultra-rare exomes 40/1,452,538 · genomes 4/152,232 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,027
South Asian	0.0325%	3,077
African / African-American	0.012%	8,304
Remaining individualsnot grpmax-eligible	0.00322%	31,093
European (non-Finnish)	8.5e-05%	1,176,143

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.Pro823Ser
Coding: c.2467C>T
MANE Select: NM_001042545
dbSNP: rs780942572
Type: single nucleotide variant
Location: chr19:40613439 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53
Residue 890 UniProt numbering: the egf-like 10; calcium-binding domain

Full LTBP4 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

LTBP4 p.Ala182Thr Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala207Val Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala23Val Uncertain significance ★★ same condition
LTBP4 p.Ala775Val Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala796Gly Uncertain significance ★★ ⚠ same condition
LTBP4 p.Ala967Pro Uncertain significance ★★ ⚠ same condition
LTBP4 p.Arg102Gly Uncertain significance ★★ ⚠ same condition
LTBP4 p.Arg193Leu 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-pro823ser (accessed [today's date]).

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