Is PLOD1 p.Arg690Ter (c.2068C>T) pathogenic?

PLOD1 p.Arg690Ter (c.2068C>T) is classified Uncertain significance in PLOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-23). Very rare (popmax 0.00401%, afr); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1.

What condition is associated with PLOD1 p.Arg690Ter (c.2068C>T)?

PLOD1 p.Arg690Ter (c.2068C>T) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1 (ClinVar).

How common is PLOD1 p.Arg690Ter (c.2068C>T) in the general population?

PLOD1 p.Arg690Ter (c.2068C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

PLOD1 p.Arg690Ter

c.2068C>T · rs373094220 · VCV644297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

Ehlers-Danlos syndrome, kyphoscoliotic type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (19 of 19) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -0.56, phastCons 0.98
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,894 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000558% 9/1,613,820 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,965
European (non-Finnish)	0.000509%	196,651

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.Arg690Ter
Coding: c.2068C>T
MANE Select: NM_000302
dbSNP: rs373094220
Type: single nucleotide variant
Location: chr1:11974692 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04
Residue 690: the fe2og dioxygenase domain

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

Disease context

Ehlers-Danlos syndrome, kyphoscoliotic type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLOD1 p.Arg690Gln Uncertain significance ★★ ⚠ same residue
PLOD1 p.Arg690Val 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-arg690ter (accessed [today's date]).

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