Is EPOR p.Pro239Arg (c.716C>G) pathogenic?

EPOR p.Pro239Arg (c.716C>G) is classified Uncertain significance in EPOR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-06). AlphaMissense: likely benign (0.1382); Ultra-rare (popmax 0.0135%, eas); Associated with Inborn genetic diseases.

What condition is associated with EPOR p.Pro239Arg (c.716C>G)?

EPOR p.Pro239Arg (c.716C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EPOR p.Pro239Arg (c.716C>G) in the general population?

EPOR p.Pro239Arg (c.716C>G) is ultra-rare (popmax 0.0135%, eas) (gnomAD).

What do computational predictors say about EPOR p.Pro239Arg (c.716C>G)?

AlphaMissense predicts likely benign (score 0.1382) — an in-silico prediction, not a clinical call.

EPOR p.Pro239Arg

c.716C>G · rs542643797 · VCV3089798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1382	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -9.15	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,220 bp · p 0.0057 · regional, not allelic
Overall
CADD	31.0	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 0.0135% East Asian · 6/44,472 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00397%

Overall 0.000437% 7/1,601,726 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0135%	7,412
Remaining individualsnot grpmax-eligible	0.00162%	61,908

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.Pro239Arg
Coding: c.716C>G
MANE Select: NM_000121
dbSNP: rs542643797
Type: single nucleotide variant
Location: chr19:11381079 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 22 PDB
Residue 239: the fibronectin type-iii domain; 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.Pro239Ser Uncertain significance ★ ⚠ same residue
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

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-pro239arg (accessed [today's date]).

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