Is EPOR c.115+7A>G pathogenic?

EPOR c.115+7A>G is classified Benign/Likely benign in EPOR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0658%, afr); Associated with primary familial polycythemia due to EPO receptor mutation.

What condition is associated with EPOR c.115+7A>G?

EPOR c.115+7A>G is associated with primary familial polycythemia due to EPO receptor mutation (ClinVar).

How common is EPOR c.115+7A>G in the general population?

EPOR c.115+7A>G is ultra-rare (popmax 0.0658%, afr) (gnomAD).

How is Primary familial polycythemia inherited?

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

EPOR c.115+7A>G

rs192525298 · VCV328156

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0658%, afr)

Conditions

primary familial polycythemia due to EPO receptor mutation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 0.3	GERP -3.8, phastCons 0.026
Overall
CADD	13.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0658% African / African-American · 48/72,904 alleles

Filtering AF 0.051% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0457%

Overall 0.0105% 161/1,537,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0658%	1,519
Middle Eastern	0.0503%	1,987
Admixed American	0.0157%	6,368
Remaining individualsnot grpmax-eligible	0.0134%	7,453
European (non-Finnish)	0.00828%	12,074

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
Coding: c.115+7A>G
MANE Select: NM_000121
dbSNP: rs192525298
Type: single nucleotide variant
Location: chr19:11384086 (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.-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
EPOR p.Asn487Ser 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-c-115-plus-7a-g (accessed [today's date]).

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