Is EGLN1 p.Pro77Ser (c.229C>T) pathogenic?

EGLN1 p.Pro77Ser (c.229C>T) is classified Uncertain significance in EGLN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-25). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.0026%, sas); Associated with erythrocytosis, familial, 3.

What condition is associated with EGLN1 p.Pro77Ser (c.229C>T)?

EGLN1 p.Pro77Ser (c.229C>T) is associated with erythrocytosis, familial, 3 (ClinVar).

How common is EGLN1 p.Pro77Ser (c.229C>T) in the general population?

EGLN1 p.Pro77Ser (c.229C>T) is very rare (popmax 0.0026%, sas) (gnomAD).

What do computational predictors say about EGLN1 p.Pro77Ser (c.229C>T)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

EGLN1 p.Pro77Ser

c.229C>T · rs920027770 · VCV1481614

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0026%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

erythrocytosis, familial, 3

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.03	unconstrained · MANE · 574 bp · p 0.59 · regional, not allelic
Overall
CADD	19.62	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 0.0026% South Asian · 2/76,974 alleles

Filtering AF 0.000431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000161%

Overall 0.000136% 2/1,465,966 alleles · very rare exomes 2/1,313,986 · genomes 0/151,980 · joint denominator

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.Pro77Ser
Coding: c.229C>T
MANE Select: NM_022051
dbSNP: rs920027770
Type: single nucleotide variant
Location: chr1:231421660 (GRCh38)
Gene constraint: LOEUF 0.739 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.81 · 67 PDB
Residue 77: 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.Pro77Leu Uncertain significance ★★ ⚠ same residue
EGLN1 p.Pro77= Likely benign ★ 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
EGLN1 p.Ala122Gly 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-pro77ser (accessed [today's date]).

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