Is LTBP2 p.Ser485Pro (c.1453T>C) pathogenic?

LTBP2 p.Ser485Pro (c.1453T>C) is classified Uncertain significance in LTBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-24). AlphaMissense: likely pathogenic (0.7976); Very rare (popmax 0.000427%, nfe).

How common is LTBP2 p.Ser485Pro (c.1453T>C) in the general population?

LTBP2 p.Ser485Pro (c.1453T>C) is very rare (popmax 0.000427%, nfe) (gnomAD).

What do computational predictors say about LTBP2 p.Ser485Pro (c.1453T>C)?

AlphaMissense predicts likely pathogenic (score 0.7976) — an in-silico prediction, not a clinical call.

LTBP2 p.Ser485Pro

c.1453T>C · rs2139746276 · VCV1380247

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7976 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000427%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7976	likely pathogenic
REVEL	0.116	moderately benign-leaning
SaProt	LLR -9.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 107 kb · p 0.013 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.000427% European (non-Finnish) · 5/1,171,882 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000312% 5/1,600,592 alleles · very rare exomes 5/1,448,336 · genomes 0/152,256 · 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: LTBP2
Protein: p.Ser485Pro
Coding: c.1453T>C
MANE Select: NM_000428
dbSNP: rs2139746276
Type: single nucleotide variant
Location: chr14:74551297 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.33

Full LTBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LTBP3 p.Asp485= Likely benign ★★ same residue
LTBP2 c.2389-2A>G Likely pathogenic ★★ same type
LTBP2 c.2659+2T>C Likely pathogenic ★★ same type
LTBP2 c.2789-1G>A Likely pathogenic ★★ same type
LTBP2 c.2789-2A>T Likely pathogenic ★★ same type
LTBP2 c.3652+1G>A Likely pathogenic ★★ same type
LTBP2 p.Arg299Ter Pathogenic ★★ same type
LTBP2 p.Cys1438Tyr Likely pathogenic ★★ same type

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/ltbp2-p-ser485pro (accessed [today's date]).

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