Is EGLN2 p.Pro248= (c.744A>T) pathogenic?

EGLN2 p.Pro248= (c.744A>T) is classified Likely benign in EGLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-11). Very rare (popmax 0.000339%, nfe).

How common is EGLN2 p.Pro248= (c.744A>T) in the general population?

EGLN2 p.Pro248= (c.744A>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

EGLN2 p.Pro248=

c.744A>T · rs1276367980 · VCV1758957

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.7
Overall
CADD	1.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,042 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,760 alleles · very rare exomes 3/1,460,510 · genomes 1/152,250 · 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: EGLN2
Protein: p.Pro248=
Coding: c.744A>T
MANE Select: NM_080732
dbSNP: rs1276367980
Type: single nucleotide variant
Location: chr19:40801316 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI 0.67 (gnomAD)
Structure: AlphaFold pLDDT 69.05 · 1 PDB

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

Similar variants

EGLN2 p.Pro248Leu Uncertain significance ★ ⚠ same residue
EGLN2 p.Pro248Ser 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

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-pro248 (accessed [today's date]).

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