Is PLOD3 p.Asp190= (c.570C>T) pathogenic?

PLOD3 p.Asp190= (c.570C>T) is classified Benign in PLOD3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.3%, nfe); Associated with bone fragility with contractures, arterial rupture, and deafness.

What condition is associated with PLOD3 p.Asp190= (c.570C>T)?

PLOD3 p.Asp190= (c.570C>T) is associated with bone fragility with contractures, arterial rupture, and deafness (ClinVar).

How common is PLOD3 p.Asp190= (c.570C>T) in the general population?

PLOD3 p.Asp190= (c.570C>T) is low-frequency (popmax 4.3%, nfe) (gnomAD).

PLOD3 p.Asp190=

Q: How is Connective tissue disorder due to lysyl hydroxylase-3 deficiency inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

c.570C>T · rs35159414 · VCV440175

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.3%, nfe)

Conditions

bone fragility with contractures, arterial rupture, and deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.108	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -0.38
Overall
CADD	3.236	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.3% European (non-Finnish) · 50,737/1,179,606 alleles

Filtering AF 4.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.26%

Overall 3.57% 57,547/1,613,204 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.5%	22
European (non-Finnish)grpmax	4.3%	23
Remaining individualsnot grpmax-eligible	3.12%	32
Finnishnot grpmax-eligible	2.66%	38
Admixed American	2.05%	49
Ashkenazi Jewishnot grpmax-eligible	1.95%	51
South Asian	0.82%	122
African / African-American	0.714%	140
Middle Eastern	0.511%	196
East Asian	0.0067%	14,931

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PLOD3
Protein: p.Asp190=
Coding: c.570C>T
MANE Select: NM_001084
dbSNP: rs35159414
Type: single nucleotide variant
Location: chr7:101215953 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.80 · 18 PDB
Residue 190: the 'required for glycosyltransferase activity' region

Full PLOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

bone fragility with contractures, arterial rupture, and deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Connective tissue disorder due to lysyl hydroxylase-3 deficiency (Orphanet):

Inheritance: Not applicable
Onset: Antenatal, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

PLOD3 c.1359-1G>C Likely pathogenic ★★ same condition
PLOD3 p.Arg452Ter Pathogenic ★★ same condition
PLOD3 p.Tyr630Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD3 p.Asp326Asn Uncertain significance ★★ ⚠ same condition
PLOD3 p.Gly224Arg Uncertain significance ★★ ⚠ same condition
PLOD3 p.Pro296Arg Uncertain significance ★★ ⚠ same condition
PLOD3 c.1233-4G>A Benign ★★ same condition
PLOD3 p.Arg468Gly Benign ★★ ⚠ 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/plod3-p-asp190 (accessed [today's date]).

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