Is LOX p.Pro87Ser (c.259C>T) pathogenic?

LOX p.Pro87Ser (c.259C>T) is classified Uncertain significance in LOX (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-21). AlphaMissense: likely benign (0.0641); Very rare (popmax 0.0018%, amr); Associated with Cardiovascular phenotype.

What condition is associated with LOX p.Pro87Ser (c.259C>T)?

LOX p.Pro87Ser (c.259C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LOX p.Pro87Ser (c.259C>T) in the general population?

LOX p.Pro87Ser (c.259C>T) is very rare (popmax 0.0018%, amr) (gnomAD).

What do computational predictors say about LOX p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

LOX p.Pro87Ser

c.259C>T · rs746215345 · VCV2777063

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0018%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -7.12	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 5.1	GERP -1, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 2,475 bp · p 0.092 · regional, not allelic
Overall
CADD	17.51	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

Grpmax group 0.0018% Admixed American · 1/55,572 alleles

Overall 0.000127% 2/1,579,376 alleles · very rare exomes 2/1,427,088 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0018%	55,572
Remaining individualsnot grpmax-eligible	0.00163%	61,310

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: LOX
Protein: p.Pro87Ser
Coding: c.259C>T
MANE Select: NM_002317
dbSNP: rs746215345
Type: single nucleotide variant
Location: chr5:122077727 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06
Residue 87: the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LOX p.Pro87Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
LOX p.Pro87Thr Uncertain significance ★ ⚠ same residue
LOX p.Pro87Arg Uncertain significance ★ ⚠ same residue
LOX p.Arg281Ter Pathogenic/Likely pathogenic ★★ same condition
LOX p.Gly202Ter Pathogenic/Likely pathogenic ★★ same condition
LOX c.1247+1G>A Uncertain significance ★★ same condition
LOX p.Ala100Thr Uncertain significance ★★ ⚠ same condition
LOX p.Ala107Thr 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/lox-p-pro87ser (accessed [today's date]).

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