Is EPOR p.Gln305Arg (c.914A>G) pathogenic?

EPOR p.Gln305Arg (c.914A>G) is classified Uncertain significance in EPOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.2377); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with EPOR p.Gln305Arg (c.914A>G)?

EPOR p.Gln305Arg (c.914A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EPOR p.Gln305Arg (c.914A>G) in the general population?

EPOR p.Gln305Arg (c.914A>G) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about EPOR p.Gln305Arg (c.914A>G)?

AlphaMissense predicts likely benign (score 0.2377) — an in-silico prediction, not a clinical call.

EPOR p.Gln305Arg

c.914A>G · VCV3509544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2377 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2377	likely benign
REVEL	0.607	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.32	donor gain · deltas
Pangolin	Δ0.29	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,220 bp · p 0.0057 · regional, not allelic
Overall
CADD	33.0	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 0.00801% African / African-American · 6/74,934 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000496% 8/1,614,086 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,489
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	8.47e-05%	1,180,030

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.Gln305Arg
Coding: c.914A>G
MANE Select: NM_000121
Type: single nucleotide variant
Location: chr19:11378692 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 22 PDB
Residue 305: 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-gln305arg (accessed [today's date]).

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