Is EGLN1 p.Pro79= (c.237G>A) pathogenic?

EGLN1 p.Pro79= (c.237G>A) is classified Likely benign in EGLN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-05). Very rare (popmax 0.00486%, amr); Associated with erythrocytosis, familial, 3.

What condition is associated with EGLN1 p.Pro79= (c.237G>A)?

EGLN1 p.Pro79= (c.237G>A) is associated with erythrocytosis, familial, 3 (ClinVar).

How common is EGLN1 p.Pro79= (c.237G>A) in the general population?

EGLN1 p.Pro79= (c.237G>A) is very rare (popmax 0.00486%, amr) (gnomAD).

EGLN1 p.Pro79=

c.237G>A · rs1656619307 · VCV1790418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00486%, amr)

Conditions

erythrocytosis, familial, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.037	GERP -2.6, phastCons 0.051
Overall
CADD	12.78	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00486% Admixed American · 2/41,122 alleles

Filtering AF 0.000806% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000302%

Overall 0.000206% 3/1,456,766 alleles · very rare exomes 2/1,304,964 · genomes 1/151,802 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00486%	20,561
Finnishnot grpmax-eligible	0.0023%	43,572

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: EGLN1
Protein: p.Pro79=
Coding: c.237G>A
MANE Select: NM_022051
dbSNP: rs1656619307
Type: single nucleotide variant
Location: chr1:231421652 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.81 · 67 PDB
Residue 79: the 'disordered' region

Full EGLN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

erythrocytosis, familial, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGLN1 p.Pro79Leu Uncertain significance ★★ ⚠ same residue
EGLN1 p.Pro79Gln Uncertain significance ★ ⚠ same residue
EGLN1 p.Pro79Thr Uncertain significance ★ ⚠ same residue
EGLN1 c.1216+6C>T Uncertain significance ★★ same condition
EGLN1 p.Ala103Val Uncertain significance ★★ ⚠ same condition
EGLN1 p.Ala114Thr Uncertain significance ★★ ⚠ same condition
EGLN1 p.Ala121Gly Uncertain significance ★★ ⚠ same condition
EGLN1 p.Ala121Pro 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/egln1-p-pro79 (accessed [today's date]).

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