Is EPOR p.Leu207Pro (c.620T>C) pathogenic?

EPOR p.Leu207Pro (c.620T>C) is classified Uncertain significance in EPOR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.8732); Ultra-rare (popmax 0.02%, mid).

How common is EPOR p.Leu207Pro (c.620T>C) in the general population?

EPOR p.Leu207Pro (c.620T>C) is ultra-rare (popmax 0.02%, mid) (gnomAD).

What do computational predictors say about EPOR p.Leu207Pro (c.620T>C)?

AlphaMissense predicts likely pathogenic (score 0.8732) — an in-silico prediction, not a clinical call.

EPOR p.Leu207Pro

c.620T>C · VCV3677577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8732	likely pathogenic · top 7% in EPOR
REVEL	0.587	indeterminate
SaProt	LLR -8.10	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,220 bp · p 0.0057 · regional, not allelic
Overall
CADD	26.9	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 0.02% Middle Eastern · 1/5,006 alleles

Overall 7.14e-05% 1/1,399,866 alleles · ultra-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.Leu207Pro
Coding: c.620T>C
MANE Select: NM_000121
Type: single nucleotide variant
Location: chr19:11381175 (GRCh38)
Gene constraint: LOEUF 0.787 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.74 · 22 PDB
Residue 207: the fibronectin type-iii domain; a β-strand

Full EPOR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPOR p.Trp439Ter Pathogenic ★★ same type
EPOR p.Glu292Lys Uncertain significance ★★ ⚠ same type
EPOR p.Pro327Leu Uncertain significance ★★ ⚠ same type
EPOR c.115+7A>G Benign/Likely benign ★★ same type
EPOR c.-55G>A Benign ★★ same type
EPOR c.*35G>A Benign ★★ same type
EPOR p.Ala186= Benign/Likely benign ★★ same type
EPOR p.Ala219= Benign ★★ same type

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-leu207pro (accessed [today's date]).

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