Is EPOR p.Trp24Arg (c.70T>C) pathogenic?

EPOR p.Trp24Arg (c.70T>C) is classified Uncertain significance in EPOR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely benign (0.2446); Very rare (popmax 0.000174%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EPOR p.Trp24Arg (c.70T>C)?

EPOR p.Trp24Arg (c.70T>C) is associated with Inborn genetic diseases (ClinVar).

How common is EPOR p.Trp24Arg (c.70T>C) in the general population?

EPOR p.Trp24Arg (c.70T>C) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about EPOR p.Trp24Arg (c.70T>C)?

AlphaMissense predicts likely benign (score 0.2446) — an in-silico prediction, not a clinical call.

EPOR p.Trp24Arg

c.70T>C · rs1231342318 · VCV2617869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2446	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,220 bp · p 0.0057 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,146,616 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000129% 2/1,549,994 alleles · very rare

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.Trp24Arg
Coding: c.70T>C
MANE Select: NM_000121
dbSNP: rs1231342318
Type: single nucleotide variant
Location: chr19:11384138 (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

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-trp24arg (accessed [today's date]).

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