Is PLOD1 p.Val596= (c.1788G>T) pathogenic?

PLOD1 p.Val596= (c.1788G>T) is classified Benign/Likely benign in PLOD1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 6.33%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Ehlers-Danlos syndrome.

PLOD1 p.Val596=

Q: What condition is associated with PLOD1 p.Val596= (c.1788G>T)?

PLOD1 p.Val596= (c.1788G>T) is associated with Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

Q: How common is PLOD1 p.Val596= (c.1788G>T) in the general population?

PLOD1 p.Val596= (c.1788G>T) is common (popmax 6.33%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1788G>T · rs35460537 · VCV263892

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 6.33%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Ehlers-Danlos syndrome

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 1.7	GERP -0.83, phastCons 1
Overall
CADD	2.354	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.33% African / African-American · 4,728/74,732 alleles

Filtering AF 6.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.11%

Overall 0.725% 11,691/1,613,122 alleles · common exomes 8,590/1,461,528 · genomes 3,101/151,594 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.33%	16
Middle Eastern	1.96%	51
South Asian	1.73%	58
Remaining individualsnot grpmax-eligible	0.893%	112
Admixed American	0.774%	129
European (non-Finnish)	0.356%	281
Finnishnot grpmax-eligible	0.0628%	1,592
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,935
East Asian	0.0112%	8,948

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: PLOD1
Protein: p.Val596=
Coding: c.1788G>T
MANE Select: NM_000302
dbSNP: rs35460537
Type: single nucleotide variant
Location: chr1:11970702 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04

Full PLOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, kyphoscoliotic type 1 familial thoracic aortic aneurysm and aortic dissection

Similar variants

PLOD1 p.Val596Met Uncertain significance ★★ ⚠ same residue
PLOD1 p.Val596Gly Uncertain significance ★ ⚠ same residue
PLOD1 c.1097+1G>A Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.1202+2T>C Likely pathogenic ★★ same condition
PLOD1 c.1470+2T>C Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.1471-2A>G Likely pathogenic ★★ same condition
PLOD1 c.1651-2A>G Pathogenic/Likely pathogenic ★★ same condition
PLOD1 c.168+1G>T Likely pathogenic ★★ 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/plod1-p-val596 (accessed [today's date]).

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