Is PLOD1 p.Phe263= (c.789C>T) pathogenic?

PLOD1 p.Phe263= (c.789C>T) is classified Likely benign in PLOD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-22). Ultra-rare (popmax 0.0164%, mid); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1.

What condition is associated with PLOD1 p.Phe263= (c.789C>T)?

PLOD1 p.Phe263= (c.789C>T) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is PLOD1 p.Phe263= (c.789C>T) in the general population?

PLOD1 p.Phe263= (c.789C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PLOD1 p.Phe263=

c.789C>T · rs908800499 · VCV529359

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -9.9	GERP -3.1
Overall
CADD	6.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000929% 15/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00223%	44,888
Finnishnot grpmax-eligible	0.00156%	64,040
African / African-American	0.00133%	74,916
South Asian	0.0011%	91,092
European (non-Finnish)	0.000847%	117,995

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.Phe263=
Coding: c.789C>T
MANE Select: NM_000302
dbSNP: rs908800499
Type: single nucleotide variant
Location: chr1:11957889 (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 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
PLOD1 c.467-2A>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-phe263 (accessed [today's date]).

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