Is ENG p.Met420fs (c.1250_1253dup) pathogenic?

ENG p.Met420fs (c.12501253dup) is classified Likely pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-02). Absent from gnomAD.

How common is ENG p.Met420fs (c.1250_1253dup) in the general population?

ENG p.Met420fs (c.1250_1253dup) is absent from gnomAD (gnomAD).

ENG p.Met420fs

c.1250_1253dup · rs1588576911 · VCV818074

Likely pathogenic Single submitter

Classification

Likely 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 9 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.99	GERP -1.8

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.Met420fs
Coding: c.1250_1253dup
MANE Select: NM_001114753
dbSNP: rs1588576911
Type: Duplication
Location: chr9:127819918 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 420: a β-strand; a disulfide bond; the zp domain

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

Similar variants

ENG p.Met420Val Uncertain significance ★★★ ⚠ same residue
ENG p.Met420Arg Uncertain significance ★ ⚠ same residue
ENG c.360+2dup Pathogenic/Likely pathogenic ★★ same type
ENG p.Ala512fs Likely pathogenic ★★ same type
ENG p.Arg199fs Pathogenic ★★ same type
ENG p.Gln166fs Pathogenic/Likely pathogenic ★★ same type
ENG p.Gln188fs Pathogenic ★★ same type
ENG p.Glu239fs 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-met420fs (accessed [today's date]).

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