Is EPO p.Pro7Ser (c.19C>T) pathogenic?

EPO p.Pro7Ser (c.19C>T) is classified Uncertain significance in EPO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.0761); Very rare (popmax 0.00167%, amr); Associated with EPO-related disorder.

What condition is associated with EPO p.Pro7Ser (c.19C>T)?

EPO p.Pro7Ser (c.19C>T) is associated with EPO-related disorder (ClinVar).

How common is EPO p.Pro7Ser (c.19C>T) in the general population?

EPO p.Pro7Ser (c.19C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about EPO p.Pro7Ser (c.19C>T)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

EPO p.Pro7Ser

c.19C>T · rs747612452 · VCV2634757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EPO-related disorder

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.42, phastCons 0.9
Overall
CADD	18.84	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 0.00167% Admixed American · 1/59,988 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00118% 19/1,613,814 alleles · very rare exomes 17/1,461,632 · genomes 2/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,988
European (non-Finnish)	0.00153%	65,554

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: EPO
Protein: p.Pro7Ser
Coding: c.19C>T
MANE Select: NM_000799
dbSNP: rs747612452
Type: single nucleotide variant
Location: chr7:100721563 (GRCh38)
Structure: AlphaFold pLDDT 90.09 · 13 PDB

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

Disease context

EPO-related disorder

Similar variants

EPO p.Pro7fs Pathogenic same residue
EPO c.-136G>A Uncertain significance same condition
EPO p.Arg137Gln Uncertain significance ⚠ same condition
EPO p.Ser147Pro Uncertain significance ⚠ same condition
EPO p.Glu116= Likely benign same condition
EPO p.Val3= Likely benign same condition
EPO c.*8del Likely benign same condition
EPO c.14-1G>C Uncertain significance ★★ 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/epo-p-pro7ser (accessed [today's date]).

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