Is GJC2 p.Pro384fs (c.1150_1151delinsA) pathogenic?

GJC2 p.Pro384fs (c.11501151delinsA) is classified Likely pathogenic in GJC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-19). Associated with GJC2-related disorder.

What condition is associated with GJC2 p.Pro384fs (c.1150_1151delinsA)?

GJC2 p.Pro384fs (c.1150_1151delinsA) is associated with GJC2-related disorder (ClinVar).

GJC2 p.Pro384fs

c.1150_1151delinsA · VCV4942315

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

GJC2-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
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.2

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

Variant & gene context

Gene: GJC2
Protein: p.Pro384fs
Coding: c.1150_1151delinsA
MANE Select: NM_020435
Type: Indel
Location: chr1:228158908 (GRCh38)
Gene constraint: LOEUF 1.604 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 68.50
Residue 384: the 'disordered' region

Full GJC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GJC2-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GJC2 p.Pro384His Uncertain significance ★★ ⚠ same residue
GJC2 p.Pro384Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
GJC2 p.Pro384Thr Uncertain significance ★ ⚠ same residue
GJC2 p.His17fs Likely pathogenic ★★ same condition
GJC2 p.Ser48Leu Pathogenic ★ same condition
GJC2 c.*5G>A Likely benign same condition
GJC2 p.Pro120= Likely benign same condition
GJC2 p.Phe8Ter 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/gjc2-p-pro384fs (accessed [today's date]).

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