Is ENG p.Glu137= (c.411G>A) pathogenic?

ENG p.Glu137= (c.411G>A) is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-28). Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Glu137= (c.411G>A)?

ENG p.Glu137= (c.411G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Glu137= (c.411G>A) in the general population?

ENG p.Glu137= (c.411G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

ENG p.Glu137=

c.411G>A · VCV4017986

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Cardiovascular phenotype

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 -3.7	GERP -3.3
Overall
CADD	1.913	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,000 alleles

Overall 0.000658% 1/152,072 alleles · very rare

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: ENG
Protein: p.Glu137=
Coding: c.411G>A
MANE Select: NM_001114753
Type: single nucleotide variant
Location: chr9:127826622 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 137: a β-strand; a disulfide bond; the 'required for interaction with gdf2' region; the 'or2' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ENG p.Glu137Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Glu137Asp Uncertain significance ★ ⚠ same residue
ENG p.Glu137Gly Uncertain significance ★ ⚠ same residue
ENG c.1134+1G>T Pathogenic/Likely pathogenic ★★ same condition
ENG c.1311+2T>A Pathogenic ★★ same condition
ENG c.1428+1G>A Pathogenic/Likely pathogenic ★★ same condition
ENG c.1687-1G>A Pathogenic/Likely pathogenic ★★ same condition
ENG c.219+1G>A Pathogenic ★★ 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/eng-p-glu137 (accessed [today's date]).

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