Is ENG p.Arg192fs (c.574_580del) pathogenic?

ENG p.Arg192fs (c.574580del) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-14). Absent from gnomAD.

How common is ENG p.Arg192fs (c.574_580del) in the general population?

ENG p.Arg192fs (c.574_580del) is absent from gnomAD (gnomAD).

ENG p.Arg192fs

c.574_580del · rs1564456347 · VCV618624

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg192fs
Coding: c.574_580del
MANE Select: NM_001114753
dbSNP: rs1564456347
Type: Deletion
Location: chr9:127825804 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 192: a disulfide bond; a UniProt-annotated variant site (in hht1); the 'required for interaction with gdf2' region; the 'or2' region

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

Similar variants

ENG p.Arg192Gly Likely benign ★★ same residue
ENG p.Arg192_Thr193insSer Uncertain significance ★ same residue
ENG p.Arg192Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Arg192His Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Arg192= Likely benign ★ same residue
ENG p.Val568fs Pathogenic ★★★ same type
ENG c.1687delG Pathogenic ★★ same type
ENG p.Ala312fs Pathogenic ★★ 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/eng-p-arg192fs (accessed [today's date]).

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