Is ERBB4 p.Cys593fs (c.1776dup) pathogenic?

ERBB4 p.Cys593fs (c.1776dup) is classified Pathogenic in ERBB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-07). Absent from gnomAD; Associated with Inborn genetic diseases.

What condition is associated with ERBB4 p.Cys593fs (c.1776dup)?

ERBB4 p.Cys593fs (c.1776dup) is associated with Inborn genetic diseases (ClinVar).

How common is ERBB4 p.Cys593fs (c.1776dup) in the general population?

ERBB4 p.Cys593fs (c.1776dup) is absent from gnomAD (gnomAD).

ERBB4 p.Cys593fs

c.1776dup · rs2469694284 · VCV2229731

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

Conditions

Inborn genetic diseases

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 15 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, 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: ERBB4
Protein: p.Cys593fs
Coding: c.1776dup
MANE Select: NM_005235
dbSNP: rs2469694284
Type: Duplication
Location: chr2:211665417 (GRCh38)
Gene constraint: LOEUF 0.357 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 73.17 · 14 PDB
Residue 593: a disulfide bond

Full ERBB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERBB4 p.Arg393Gln Uncertain significance ★★ ⚠ same condition
ERBB4 p.Gln598Lys Uncertain significance ★★ ⚠ same condition
ERBB4 p.Glu1138Gly Uncertain significance ★★ ⚠ same condition
ERBB4 p.Glu696Ala Uncertain significance ★★ ⚠ same condition
ERBB4 p.Ile337Val Uncertain significance ★★ ⚠ same condition
ERBB4 p.Lys291Arg Uncertain significance ★★ ⚠ same condition
ERBB4 p.Lys681Arg Uncertain significance ★★ ⚠ same condition
ERBB4 p.Lys873Thr Uncertain significance ★★ ⚠ 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/erbb4-p-cys593fs (accessed [today's date]).

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