Is EPOR p.Pro250Arg (c.749C>G) pathogenic?

EPOR p.Pro250Arg (c.749C>G) is classified Uncertain significance in EPOR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: ambiguous (0.3777); Very rare (popmax 0.00157%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EPOR p.Pro250Arg (c.749C>G)?

EPOR p.Pro250Arg (c.749C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EPOR p.Pro250Arg (c.749C>G) in the general population?

EPOR p.Pro250Arg (c.749C>G) is very rare (popmax 0.00157%, nfe) (gnomAD).

What do computational predictors say about EPOR p.Pro250Arg (c.749C>G)?

AlphaMissense predicts ambiguous (score 0.3777) — an in-silico prediction, not a clinical call.

EPOR p.Pro250Arg

c.749C>G · VCV4018938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00157%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3777	ambiguous
REVEL	0.616	indeterminate
SaProt	LLR -8.79	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,220 bp · p 0.0057 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00157% European (non-Finnish) · 18/1,147,566 alleles

Filtering AF 0.00098% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000809%

Overall 0.00136% 19/1,400,716 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00166%	60,174
European (non-Finnish)grpmax	0.00157%	63,754

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro250Arg
Coding: c.749C>G
MANE Select: NM_000121
Type: single nucleotide variant
Location: chr19:11380962 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 22 PDB
Residue 250: an α-helix

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

Similar variants

EPOR p.Glu292Lys Uncertain significance ★★ ⚠ same condition
EPOR p.Pro327Leu Uncertain significance ★★ ⚠ same condition
EPOR p.Asp482Asn Likely benign ★★ same condition
EPOR p.Pro347= Benign/Likely benign ★★ same condition
EPOR p.Ala147Val Uncertain significance ★ ⚠ same condition
EPOR p.Ala20Ser Uncertain significance ★ ⚠ same condition
EPOR p.Ala219Thr Uncertain significance ★ ⚠ same condition
EPOR p.Ala270Thr Uncertain significance ★ ⚠ 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-pro250arg (accessed [today's date]).

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