Is ENG p.Ile114= (c.342C>T) pathogenic?

ENG p.Ile114= (c.342C>T) is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Very rare (popmax 0.005%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Ile114= (c.342C>T)?

ENG p.Ile114= (c.342C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Ile114= (c.342C>T) in the general population?

ENG p.Ile114= (c.342C>T) is very rare (popmax 0.005%, amr) (gnomAD).

ENG p.Ile114=

c.342C>T · VCV3508498

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, 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 1.8	GERP 0.45, phastCons 1
Overall
CADD	7.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,978 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000372% 6/1,613,998 alleles · very rare exomes 4/1,461,808 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,993
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	8.47e-05%	1,180,011

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.Ile114=
Coding: c.342C>T
MANE Select: NM_001114753
Type: single nucleotide variant
Location: chr9:127829705 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 114: 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 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
ENG c.219+2T>C Pathogenic/Likely pathogenic ★★ same condition
ENG c.360+1G>A Pathogenic ★★ same condition
ENG c.360+1G>C 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-ile114 (accessed [today's date]).

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