Is EPOR p.Trp439Ter (c.1317G>A) pathogenic?

EPOR p.Trp439Ter (c.1317G>A) is classified Pathogenic in EPOR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-05-20). Absent from gnomAD v4.1; Associated with EPOR-related disorder.

What condition is associated with EPOR p.Trp439Ter (c.1317G>A)?

EPOR p.Trp439Ter (c.1317G>A) is associated with EPOR-related disorder, primary familial polycythemia due to EPO receptor mutation (ClinVar).

How common is EPOR p.Trp439Ter (c.1317G>A) in the general population?

EPOR p.Trp439Ter (c.1317G>A) is absent from gnomAD v4.1 (gnomAD).

EPOR p.Trp439Ter

c.1317G>A · rs121918116 · VCV16595

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

EPOR-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.07	GERP -3.7, phastCons 0.002
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPOR
Protein: p.Trp439Ter
Coding: c.1317G>A
MANE Select: NM_000121
dbSNP: rs121918116
Type: single nucleotide variant
Location: chr19:11378194 (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

EPOR-related disorder

Also linked: primary familial polycythemia due to EPO receptor mutation

Similar variants

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
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-p-trp439ter (accessed [today's date]).

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