Is PLOD1 p.Ser431= (c.1293C>T) pathogenic?

PLOD1 p.Ser431= (c.1293C>T) is classified Likely benign in PLOD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-01). Ultra-rare (popmax 0.0169%, sas); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1.

What condition is associated with PLOD1 p.Ser431= (c.1293C>T)?

PLOD1 p.Ser431= (c.1293C>T) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PLOD1 p.Ser431= (c.1293C>T) in the general population?

PLOD1 p.Ser431= (c.1293C>T) is ultra-rare (popmax 0.0169%, sas) (gnomAD).

PLOD1 p.Ser431=

c.1293C>T · rs776976856 · VCV1574726

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -5.6
Overall
CADD	0.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% South Asian · 15/88,702 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00842%

Overall 0.0016% 23/1,441,510 alleles · ultra-rare exomes 22/1,305,400 · genomes 1/136,110 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0169%	5,913
East Asian	0.00329%	30,388
European (non-Finnish)	0.000651%	153,511

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.Ser431=
Coding: c.1293C>T
MANE Select: NM_000302
dbSNP: rs776976856
Type: single nucleotide variant
Location: chr1:11964265 (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, kyphoscoliotic type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

Similar variants

PLOD1 p.Ser431Phe 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
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-ser431 (accessed [today's date]).

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