Is LTBP4 p.Pro55Ser (c.163C>T) pathogenic?

LTBP4 p.Pro55Ser (c.163C>T) is classified Uncertain significance in LTBP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0865); Very rare (popmax 0.00568%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LTBP4 p.Pro55Ser (c.163C>T)?

LTBP4 p.Pro55Ser (c.163C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LTBP4 p.Pro55Ser (c.163C>T) in the general population?

LTBP4 p.Pro55Ser (c.163C>T) is very rare (popmax 0.00568%, nfe) (gnomAD).

What do computational predictors say about LTBP4 p.Pro55Ser (c.163C>T)?

AlphaMissense predicts likely benign (score 0.0865) — an in-silico prediction, not a clinical call.

LTBP4 p.Pro55Ser

c.163C>T · rs201169987 · VCV1194888

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0865	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.81	GERP -0.89
Overall
CADD	6.404	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P92S vs ClinVar P55S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00568% European (non-Finnish) · 67/1,179,874 alleles

Filtering AF 0.00454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00465% 75/1,613,632 alleles · very rare exomes 71/1,461,484 · genomes 4/152,148 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,610
East Asian	0.00445%	22,448
African / African-American	0.00267%	37,452
South Asian	0.0022%	45,542
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Pro55Ser
Coding: c.163C>T
MANE Select: NM_001042545 · reported on NM_003573
dbSNP: rs201169987
Type: single nucleotide variant
Location: chr19:40599489 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.53

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-pro55ser (accessed [today's date]).

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