Is EGLN2 p.Val183= (c.549G>T) pathogenic?

EGLN2 p.Val183= (c.549G>T) is classified Likely benign in EGLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Ultra-rare (popmax 0.0165%, mid).

How common is EGLN2 p.Val183= (c.549G>T) in the general population?

EGLN2 p.Val183= (c.549G>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

EGLN2 p.Val183=

c.549G>T · rs1328742109 · VCV1747919

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 5.1	phastCons 1
Overall
CADD	11.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000248% 4/1,612,798 alleles · ultra-rare exomes 4/1,460,416 · genomes 0/152,382 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,249
European (non-Finnish)	8.48e-05%	1,179,928

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: EGLN2
Protein: p.Val183=
Coding: c.549G>T
MANE Select: NM_080732
dbSNP: rs1328742109
Type: single nucleotide variant
Location: chr19:40801121 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 69.05 · 1 PDB
Residue 183: an α-helix

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

Similar variants

EGLN2 p.Val183Leu Uncertain significance ★ ⚠ 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-val183 (accessed [today's date]).

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