Is EPOR c.*577A>G pathogenic?

EPOR c.577A>G is classified Benign in EPOR (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.869%, eas); Associated with primary familial polycythemia due to EPO receptor mutation.

What condition is associated with EPOR c.*577A>G?

EPOR c.*577A>G is associated with primary familial polycythemia due to EPO receptor mutation (ClinVar).

How common is EPOR c.*577A>G in the general population?

EPOR c.*577A>G is rare (popmax 0.869%, eas) (gnomAD).

How is Primary familial polycythemia inherited?

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

EPOR c.*577A>G

rs141524122 · VCV328133

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.869%, eas)

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 -0.055	GERP -1.6
Non-coding constraint	Z 1.66	1 kb window · o/e 0.88 · regional · uncalibrated
Overall
CADD	3.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.869% East Asian · 125/14,390 alleles

Filtering AF 0.745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.698%

Overall 0.0317% 144/454,026 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.869%	115
Remaining individualsnot grpmax-eligible	0.0248%	4,040
African / African-American	0.022%	4,554
Admixed American	0.00235%	42,554
European (non-Finnish)	0.00132%	75,589

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.*577A>G
MANE Select: NM_000121
dbSNP: rs141524122
Type: single nucleotide variant
Location: chr19:11377407 (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-c-star-577a-g (accessed [today's date]).

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