Is EPOR p.Pro347= (c.1041G>A) pathogenic?

EPOR p.Pro347= (c.1041G>A) is classified Benign/Likely benign in EPOR (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). Rare (popmax 0.759%, mid); Associated with Inborn genetic diseases.

What condition is associated with EPOR p.Pro347= (c.1041G>A)?

EPOR p.Pro347= (c.1041G>A) is associated with Inborn genetic diseases, primary familial polycythemia due to EPO receptor mutation (ClinVar).

How common is EPOR p.Pro347= (c.1041G>A) in the general population?

EPOR p.Pro347= (c.1041G>A) is rare (popmax 0.759%, mid) (gnomAD).

EPOR p.Pro347=

c.1041G>A · rs138884102 · VCV328144

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.759%, mid)

Conditions

Inborn genetic diseases

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 -6.1	GERP -3.9
Overall
CADD	0.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.759% Middle Eastern · 46/6,062 alleles

Filtering AF 0.585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.523%

Overall 0.109% 1,756/1,614,192 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.759%	132
Ashkenazi Jewishnot grpmax-eligible	0.649%	154
Remaining individualsnot grpmax-eligible	0.168%	595
Admixed American	0.128%	780
South Asian	0.124%	806
European (non-Finnish)	0.101%	990
Finnishnot grpmax-eligible	0.0203%	4,925
African / African-American	0.02%	5,003
East Asian	0.00668%	14,961

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.Pro347=
Coding: c.1041G>A
MANE Select: NM_000121
dbSNP: rs138884102
Type: single nucleotide variant
Location: chr19:11378470 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary familial polycythemia due to EPO receptor mutation

Similar variants

EPOR p.Trp439Ter Pathogenic ★★ same condition
EPOR p.Glu292Lys Uncertain significance ★★ ⚠ 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

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-pro347 (accessed [today's date]).

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