Is EPOR p.Leu8= (c.24C>T) pathogenic?

EPOR p.Leu8= (c.24C>T) is classified Benign/Likely benign in EPOR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-05-21). Low-frequency (popmax 1.77%, sas); Associated with primary familial polycythemia due to EPO receptor mutation.

What condition is associated with EPOR p.Leu8= (c.24C>T)?

EPOR p.Leu8= (c.24C>T) is associated with primary familial polycythemia due to EPO receptor mutation (ClinVar).

How common is EPOR p.Leu8= (c.24C>T) in the general population?

EPOR p.Leu8= (c.24C>T) is low-frequency (popmax 1.77%, sas) (gnomAD).

How is Primary familial polycythemia inherited?

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

EPOR p.Leu8=

c.24C>T · rs577368929 · VCV328157

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.77%, sas)

Conditions

primary familial polycythemia due to EPO receptor mutation

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 -3.5, phastCons 0.059
Overall
CADD	0.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.77% South Asian · 1,485/84,032 alleles

Filtering AF 1.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.66%

Overall 0.103% 1,591/1,548,084 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.77%	57
Remaining individualsnot grpmax-eligible	0.142%	706
Middle Eastern	0.0862%	1,160
African / African-American	0.0109%	9,146
East Asian	0.00244%	40,902
European (non-Finnish)	0.00061%	163,801

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: EPOR
Protein: p.Leu8=
Coding: c.24C>T
MANE Select: NM_000121
dbSNP: rs577368929
Type: single nucleotide variant
Location: chr19:11384184 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 22 PDB

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

Disease context

primary familial polycythemia due to EPO receptor mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary familial polycythemia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

EPOR p.Trp439Ter Pathogenic ★★ same condition
EPOR p.Pro327Leu Uncertain significance ★★ ⚠ same condition
EPOR c.115+7A>G Benign/Likely benign ★★ same condition
EPOR c.-55G>A Benign ★★ same condition
EPOR c.*35G>A Benign ★★ same condition
EPOR p.Ala186= Benign/Likely benign ★★ same condition
EPOR p.Ala219= Benign ★★ same condition
EPOR p.Arg56= Benign/Likely benign ★★ 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/epor-p-leu8 (accessed [today's date]).

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