Is PLOD1 p.Phe98= (c.294C>T) pathogenic?

PLOD1 p.Phe98= (c.294C>T) is classified Benign in PLOD1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 42.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with PLOD1 p.Phe98= (c.294C>T)?

PLOD1 p.Phe98= (c.294C>T) is associated with familial thoracic aortic aneurysm and aortic dissection, Ehlers-Danlos syndrome, kyphoscoliotic type 1 (ClinVar).

PLOD1 p.Phe98=

Q: How common is PLOD1 p.Phe98= (c.294C>T) in the general population?

PLOD1 p.Phe98= (c.294C>T) is common (popmax 42.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.294C>T · rs7529452 · VCV255803

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 42.8%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 1.1	GERP -2, phastCons 1
Overall
CADD	13.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.8% South Asian · 38,989/91,066 alleles

Filtering AF 42.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.3%

Overall 31.1% 501,873/1,613,408 alleles · common exomes 463,265/1,461,332 · genomes 38,608/152,076 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	44.4%	2
South Asiangrpmax	42.8%	2
East Asian	34.7%	3
Admixed American	33.5%	3
European (non-Finnish)	31.1%	3
Remaining individualsnot grpmax-eligible	30.8%	3
Middle Eastern	30.8%	3
Ashkenazi Jewishnot grpmax-eligible	22%	5
Amishnot grpmax-eligible	13.8%	7
African / African-American	5.93%	17

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe98=
Coding: c.294C>T
MANE Select: NM_000302
dbSNP: rs7529452
Type: single nucleotide variant
Location: chr1:11949898 (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

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, kyphoscoliotic type 1

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

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-phe98 (accessed [today's date]).

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