Is PLOD1 p.Val643= (c.1929C>T) pathogenic?

PLOD1 p.Val643= (c.1929C>T) is classified Likely benign in PLOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-10). Very rare (popmax 0.0011%, sas); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1.

What condition is associated with PLOD1 p.Val643= (c.1929C>T)?

PLOD1 p.Val643= (c.1929C>T) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1 (ClinVar).

How common is PLOD1 p.Val643= (c.1929C>T) in the general population?

PLOD1 p.Val643= (c.1929C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

PLOD1 p.Val643=

c.1929C>T · rs752137195 · VCV1130705

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Ehlers-Danlos syndrome, kyphoscoliotic type 1

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 0.23	GERP -2.7, phastCons 0.97
Overall
CADD	8.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,086 alleles

Overall 6.2e-05% 1/1,614,106 alleles · very rare exomes 1/1,461,812 · genomes 0/152,294 · joint denominator

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.Val643=
Coding: c.1929C>T
MANE Select: NM_000302
dbSNP: rs752137195
Type: single nucleotide variant
Location: chr1:11972898 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04
Residue 643: 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.Val643Ile Conflicting classifications of pathogenicity ★ 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
PLOD1 c.1903-2A>G 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-val643 (accessed [today's date]).

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