Is ENG p.Ala512fs (c.1531_1534dup) pathogenic?

ENG p.Ala512fs (c.15311534dup) is classified Likely pathogenic in ENG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-09). Associated with ENG-related disorder.

What condition is associated with ENG p.Ala512fs (c.1531_1534dup)?

ENG p.Ala512fs (c.1531_1534dup) is associated with ENG-related disorder (ClinVar).

ENG p.Ala512fs

c.1531_1534dup · VCV3336866

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ENG-related disorder

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 12 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: ENG
Protein: p.Ala512fs
Coding: c.1531_1534dup
MANE Select: NM_001114753
Type: Duplication
Location: chr9:127818271 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 512: the zp domain

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

Disease context

ENG-related disorder

Similar variants

ENG p.Val133fs Pathogenic ★★ same condition
ENG p.Cys516fs Likely pathogenic ★ same condition
ENG p.Ala512Thr Uncertain significance ★ ⚠ same residue
ENG p.Ala512Val Uncertain significance ★ ⚠ same residue
ENG p.Ala512= Likely benign ★ same residue
ENG c.1686+1G>A Pathogenic ★★ same condition
ENG c.1687delG Pathogenic ★★ same condition
ENG c.-127C>T 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-ala512fs (accessed [today's date]).

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