Is ENG p.Thr383= (c.1149C>T) pathogenic?

ENG p.Thr383= (c.1149C>T) is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Thr383= (c.1149C>T)?

ENG p.Thr383= (c.1149C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Thr383= (c.1149C>T) in the general population?

ENG p.Thr383= (c.1149C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

ENG p.Thr383=

c.1149C>T · VCV4614106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 0.81	GERP 0.5, phastCons 0.003
Overall
CADD	6.308	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,048 alleles

Overall 0.000124% 2/1,614,046 alleles · very rare exomes 2/1,461,748 · genomes 0/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,048
European (non-Finnish)	8.47e-05%	1,180,038

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.Thr383=
Coding: c.1149C>T
MANE Select: NM_001114753
Type: single nucleotide variant
Location: chr9:127820023 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 383: the zp domain

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.Thr383Ala Uncertain significance ★ ⚠ same residue
ENG p.Thr383Ser 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
ENG c.219+2T>C 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-thr383 (accessed [today's date]).

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