Is EGLN2 p.Pro75Arg (c.224C>G) pathogenic?

EGLN2 p.Pro75Arg (c.224C>G) is classified Uncertain significance in EGLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). AlphaMissense: likely benign (0.0839); Absent from gnomAD v4.1.

How common is EGLN2 p.Pro75Arg (c.224C>G) in the general population?

EGLN2 p.Pro75Arg (c.224C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGLN2 p.Pro75Arg (c.224C>G)?

AlphaMissense predicts likely benign (score 0.0839) — an in-silico prediction, not a clinical call.

EGLN2 p.Pro75Arg

c.224C>G · rs1599758188 · VCV1788393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0839 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0839	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.98	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 6	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 830 bp · p 0.68 · regional, not allelic
Overall
CADD	22.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EGLN2
Protein: p.Pro75Arg
Coding: c.224C>G
MANE Select: NM_080732
dbSNP: rs1599758188
Type: single nucleotide variant
Location: chr19:40800796 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 69.05 · 1 PDB
Residue 75: the 'disordered' region

Full EGLN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EGLN2 p.Pro75= Likely benign ★ same residue
EGLN2 p.Ala137Thr Uncertain significance ★★ ⚠ same type
EGLN2 p.Arg236Cys Uncertain significance ★★ ⚠ same type
EGLN2 p.Arg306Cys Uncertain significance ★★ ⚠ same type
EGLN2 c.1100+23C>A Benign ★★ same type
EGLN2 c.844-141G>A Benign ★★ same type
EGLN2 c.844-199G>A Benign ★★ same type
EGLN2 c.963+33G>C 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/egln2-p-pro75arg (accessed [today's date]).

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