Is LOX p.Pro72= (c.216G>A) pathogenic?

LOX p.Pro72= (c.216G>A) is classified Benign/Likely benign in LOX (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Rare (popmax 0.118%, mid); Associated with Cardiovascular phenotype.

What condition is associated with LOX p.Pro72= (c.216G>A)?

LOX p.Pro72= (c.216G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is LOX p.Pro72= (c.216G>A) in the general population?

LOX p.Pro72= (c.216G>A) is rare (popmax 0.118%, mid) (gnomAD).

LOX p.Pro72=

c.216G>A · rs753662323 · VCV1209132

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.118%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -3.5
Overall
CADD	5.385	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.118% Middle Eastern · 7/5,936 alleles

Filtering AF 0.0553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.00568% 88/1,548,584 alleles · rare exomes 83/1,396,556 · genomes 5/152,028 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.118%	848
South Asian	0.0553%	1,808
Remaining individualsnot grpmax-eligible	0.0149%	6,691
Admixed American	0.00778%	12,856
European (non-Finnish)	0.00174%	57,581
African / African-American	0.00137%	73,112

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.Pro72=
Coding: c.216G>A
MANE Select: NM_002317
dbSNP: rs753662323
Type: single nucleotide variant
Location: chr5:122077770 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 68.06
Residue 72: 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.Pro72Arg Uncertain significance ★★ ⚠ same residue
LOX p.Pro72Leu Uncertain significance ★ ⚠ same residue
LOX p.Pro72Thr 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-pro72 (accessed [today's date]).

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