Is ENG p.Met1Ile (c.3G>T) pathogenic?

ENG p.Met1Ile (c.3G>T) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-18). No allele count reported in gnomAD v4.1 (AN 1,588,866); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Met1Ile (c.3G>T)?

ENG p.Met1Ile (c.3G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Met1Ile (c.3G>T) in the general population?

ENG p.Met1Ile (c.3G>T) is no allele count reported in gnomAD v4.1 (AN 1,588,866) (gnomAD).

ENG p.Met1Ile

c.3G>T · rs2539126528 · VCV1736912

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,866)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
REVEL	0.399	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,588,866). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENG
Protein: p.Met1Ile
Coding: c.3G>T
MANE Select: NM_001114753
dbSNP: rs2539126528
Type: single nucleotide variant
Location: chr9:127854353 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB

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.Met1Thr Pathogenic ★★ same residue
ENG p.Met1fs Pathogenic ★ same residue
ENG p.Met1Arg Pathogenic ★★★ same residue
ENG p.Met1Val Pathogenic ★★ same residue
ENG p.Met1Leu Pathogenic ★ 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

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-met1ile (accessed [today's date]).

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